Peroxisomes in brain development and function

In the paper

“Patients lacking either all peroxisomal functions or a single enzyme or transporter function typically develop severe neurological deficits”

In the paper

“During early stages of murine peripheral nerve (sciatic nerve) myelination, peroxisomes appear to be diffusely distributed in the myelin sheath of Schwann cells, whereas at later stages, peroxisomes were found to be enriched in the myelin loops of the paranodal region [14].”

What the sources say

• Not checked yetcites [14] Kassmann CM Quintes S Rietdorf J Mobius W Sereda MW Nientiedt T Saher G Baes M Nave KA A role for myelin-associated peroxisomes in maintaining paranodal loops and axonal integrity FEBS Lett 2011 585 2205 2211 21620837 source

In the paper

“The symptoms of patients with peroxisomal single enzyme and transporter deficiencies have a broad heterogeneity, related to differences in the physiological role of the affected metabolic pathway or reaction [5].”

What the sources say

• Not checked yetcites [5] Mi J Kirchner E Cristobal S Quantitative proteomic comparison of mouse peroxisomes from liver and kidney Proteomics 2007 7 1916 1928 17474143 source

In the paper

“In the brain, peroxisomes appear as electron-dense single membrane-bound organelles that have been detected in all neural cell types, namely in neurons [13], oligodendrocytes [14,15] and astrocytes [13] and microglia and endothelial cells [16].”

What the sources say

• Not checked yetcites [13] Arnold G Liscum L Holtzman E Ultrastructural localization of D-amino acid oxidase in microperoxisomes of the rat nervous system J Histochem Cytochem 1979 27 735 745 39097 source
• Not checked yetcites [14] Kassmann CM Quintes S Rietdorf J Mobius W Sereda MW Nientiedt T Saher G Baes M Nave KA A role for myelin-associated peroxisomes in maintaining paranodal loops and axonal integrity FEBS Lett 2011 585 2205 2211 21620837 source
• Not checked yetcites [15] Houdou S Kuruta H Hasegawa M Konomi H Takashima S Suzuki Y Hashimoto T Developmental immunohistochemistry of catalase in the human brain Brain Res 1991 556 267 270 1933360 source
• Not checked yetcites [16] Fouquet F Zhou JM Ralston E Murray K Troalen F Magal E Robain O Dubois-Dalcq M Aubourg P Expression of the adrenoleukodystrophy protein in the human and mouse central nervous system Neurobiol Dis 1997 3 271 285 9173925 source

In the paper

“Accordingly, metabolic dysfunction associated with a complete loss of all peroxisomal functions or of individual enzymatic reactions is often linked to perturbation of brain formation, function or maintenance.”

In the paper

“On the one hand, peroxisomes generate building blocks (intermediates) for the biosynthesis of complex lipids such as ether phospholipids, which are important components of myelin, the membrane processes of oligodendrocytes that ensheath and isolate axons.”

In the paper

“This is the reason why in Zellweger spectrum patients, on the cellular level, peroxisomes are either absent or empty (ghosts).”

In the paper

“In neurons of human dorsal root ganglia, peroxisomes were readily detected based on immunohistochemistry for ABCD1 [30].”

What the sources say

• Not checked yetcites [30] Hoftberger R Kunze M Weinhofer I Aboul-Enein F Voigtlander T Oezen I Amann G Bernheimer H Budka H Berger J Distribution and cellular localization of adrenoleukodystrophy protein in human tissues: implications for X-linked adrenoleukodystrophy Neurobiol Dis 2007 28 165 174 17761426 source

In the paper

“In the rat PNS, peroxisomes were described in Schwann cells, which represent the myelinating cells of the PNS, as well as in dorsal root ganglion satellite cells and, less abundantly, in neuronal somata [29].”

What the sources say

• Not checked yetcites [29] Citkowitz E Holtzman E Peroxisomes in dorsal root ganglia J Histochem Cytochem 1973 21 34 41 4694538 source

In the paper

“which originate from aberrant development of the brain, demyelination and loss of axonal integrity, neuroinflammation or other neurodegenerative processes”

In the paper

“The brain pathology in peroxisomal disorders can be grouped into three major classes: i) abnormalities in neuronal migration or differentiation, ii) defects in the formation or maintenance of central white matter, and iii) post-developmental neuronal degeneration [6].”

What the sources say

• Not checked yetcites [6] Powers JM Moser HW Peroxisomal disorders: genotype, phenotype, major neuropathologic lesions, and pathogenesis Brain Pathol 1998 8 101 120 9458170 PMC8098283 source

In the paper

“The genetic basis for each PBD is a mutation in one of 14 PEX genes, which encode proteins termed peroxins (PEX proteins or peroxisome biogenesis factors), which are involved in the biogenesis of the organelle (Table 1).”

In the paper

“Moreover, peroxisomes exert the last step in the biosynthesis of the very long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA; C22:6 n-3), which has important roles in the nervous system [11].”

What the sources say

• Not checked yetcites [11] Dyall SC Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA Front Aging Neurosci 2015 7 52 25954194 PMC4404917 source

In the paper

“On the other hand, peroxisomes degrade toxic compounds that can either interfere with proper brain formation or damage brain structures (e.g., phytanic acid).”

In the paper

“Furthermore, peroxisomal enzymes degrade D-amino acids such as D-aspartate and D-serine, which modulate synaptic signaling by altering the efficiency of synaptic transmission (Fig. 3A, left panel).”

In the paper

“In this study, it was found that peroxisomal activities decreased during postnatal development (P2, P15, P49), irrespective of whether the activity was normalized to the whole brain or to different brain regions (cerebellum, hippocampus, cortex) [19].”

What the sources say

• Not checked yetcites [19] Ahlemeyer B Neubert I Kovacs WJ Baumgart-Vogt E Differential expression of peroxisomal matrix and membrane proteins during postnatal development of mouse brain J Comp Neurol 2007 505 1 17 17729295 source

In the paper

“In the murine brain, the mRNA levels of the peroxisomal β-oxidation enzymes (ACOX1, DBP, ACAA1a), the ABC transporters ABCD2 and ABCD3, and the enzymes involved in ether phospholipid biosynthesis increased after birth, reached a maximum during the first weeks and then declined.”

What the sources say

• Not checked yetcites [26] Knoll A Sargueil F Salles J Cassagne C Garbay B Gene expression of peroxisomal beta-oxidation enzymes in rat brain Brain Res Mol Brain Res 1999 74 217 220 10640693 source
• Not checked yetcites [27] Huyghe S Casteels M Janssen A Meulders L Mannaerts GP Declercq PE Van Veldhoven PP Baes M Prenatal and postnatal development of peroxisomal lipid-metabolizing pathways in the mouse Biochem J 2001 353 673 680 11171065 PMC1221614 source
• Not checked yetcites [28] Berger J Albet S Bentejac M Netik A Holzinger A Roscher AA Bugaut M Forss-Petter S The four murine peroxisomal ABC-transporter genes differ in constitutive, inducible and developmental expression Eur J Biochem 1999 265 719 727 10504404 source

In the paper

“Thus, pathological aberrations of the nervous system are prominent features in most peroxisomal disorders”

In the paper

“which exert a variety of catabolic and anabolic reactions as, for example, the degradation of very long-chain fatty acids (VLCFA)1, dicarboxylic acids, branched-chain fatty acids, or parts of the biosynthesis of ether phospholipids or specific polyunsaturated fatty acids [3]”

What the sources say

• Not checked yetcites [3] Wanders RJ Waterham HR Biochemistry of mammalian peroxisomes revisited Annu Rev Biochem 2006 75 295 332 16756494 source

In the paper

“In some cases, mild initial symptoms are later followed by severe CNS demyelination and death of the patient [53,55,56].”

What the sources say

• Not checked yetcites [53] Weller S Rosewich H Gartner J Cerebral MRI as a valuable diagnostic tool in Zellweger spectrum patients J Inherit Metab Dis 2008 31 270 280 18415699 source
• Not checked yetcites [55] Barkovich AJ Peck WW MR of Zellweger syndrome AJNR Am J Neuroradiol 1997 18 1163 1170 9194444 PMC8337298
• Not checked yetcites [56] Baes M Aubourg P Peroxisomes, myelination, and axonal integrity in the CNS Neuroscientist 2009 15 367 379 19666893 source

In the paper

“Furthermore, the absence of one or more peroxisomal functions can indirectly increase the level of intracellular ROS, because under such conditions, the accumulation of particular compounds such as VLCFAs could be linked to disturbances in mitochondrial integrity, which secondarily increases the production rate of ROS [43,44].”

What the sources say

• Not checked yetcites [43] Fourcade S Lopez-Erauskin J Ruiz M Ferrer I Pujol A Mitochondrial dysfunction and oxidative damage cooperatively fuel axonal degeneration in X-linked adrenoleukodystrophy Biochimie 2014 98 143 149 24076127 source
• Not checked yetcites [44] Zorov DB Juhaszova M Sollott SJ Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release Physiol Rev 2014 94 909 950 24987008 PMC4101632 source

In the paper

“In the mildest forms of the Zellweger spectrum, patients can survive into adulthood [47,58,59].”

What the sources say

• Not checked yetcites [47] Berendse K Engelen M Ferdinandusse S Majoie CB Waterham HR Vaz FM Koelman JH Barth PG Wanders RJ Poll-The BT Zellweger spectrum disorders: clinical manifestations in patients surviving into adulthood J Inherit Metab Dis 2015 PMC4710674 26287655
• Not checked yetcites [58] Ebberink MS Csanyi B Chong WK Denis S Sharp P Mooijer PA Dekker CJ Spooner C Ngu LH De Sousa C Wanders RJ Identification of an unusual variant peroxisome biogenesis disorder caused by mutations in the PEX16 gene J Med Genet 2010 47 608 615 20647552 source
• Not checked yetcites [59] Sevin C Ferdinandusse S Waterham HR Wanders RJ Aubourg P Autosomal recessive cerebellar ataxia caused by mutations in the PEX2 gene, Orphanet J Rare Dis 2011 6 8 PMC3064617 21392394 source

In the paper

“Exogenously added palmitate can stimulate H2O2 production in peroxisomes of insulin-producing cells [34]”

What the sources say

• Not checked yetcites [34] Elsner M Gehrmann W Lenzen S Peroxisome-generated hydrogen peroxide as important mediator of lipotoxicity in insulin-producing cells Diabetes 2011 60 200 208 20971967 PMC3012172 source

In the paper

“The abnormalities in the cytoarchitecture of the cerebral cortex are usually bilateral and approximately symmetrical [49,50].”

What the sources say

• Not checked yetcites [49] Volpe JJ Adams RD Cerebro-hepato-renal syndrome of Zellweger: an inherited disorder of neuronal migration Acta Neuropathol 1972 20 175 198 5043999 source
• Not checked yetcites [50] Evrard P Caviness VS Jr Prats-Vinas J Lyon G The mechanism of arrest of neuronal migration in the Zellweger malformation: an hypothesis bases upon cytoarchitectonic analysis Acta Neuropathol 1978 41 109 117 636841 source

In the paper

“In the cerebellum of one case, overabundance of reactive astrocytes in the white matter was associated with perivascular cuffs of mononuclear cells [57].”

What the sources say

• Not checked yetcites [57] Aubourg P Scotto J Rocchiccioli F Feldmann-Pautrat D Robain O Neonatal adrenoleukodystrophy J Neurol Neurosurg Psychiatry 1986 49 77 86 2420940 PMC1028652 source

In the paper

“Less severe cerebral migratory abnormalities were reported in neonatal adrenoleukodystrophy [51].”

What the sources say

• Not checked yetcites [51] Kelley RI Datta NS Dobyns WB Hajra AK Moser AB Noetzel MJ Zackai EH Moser HW Neonatal adrenoleukodystrophy: new cases, biochemical studies, and differentiation from Zellweger and related peroxisomal polydystrophy syndromes Am J Med Genet 1986 23 869 901 3515938 source

In the paper

“In recent years, increasing numbers of patients have been described with a later onset of the disease [47].”

What the sources say

• Not checked yetcites [47] Berendse K Engelen M Ferdinandusse S Majoie CB Waterham HR Vaz FM Koelman JH Barth PG Wanders RJ Poll-The BT Zellweger spectrum disorders: clinical manifestations in patients surviving into adulthood J Inherit Metab Dis 2015 PMC4710674 26287655

In the paper

“Heterotopic Purkinje cells were found to be aggregated in irregular clumps in the subcortical areas of the cerebellar cortex in two of the three cases [57].”

What the sources say

• Not checked yetcites [57] Aubourg P Scotto J Rocchiccioli F Feldmann-Pautrat D Robain O Neonatal adrenoleukodystrophy J Neurol Neurosurg Psychiatry 1986 49 77 86 2420940 PMC1028652 source

In the paper

“Neuropathological examination of brains obtained from three cases of neonatal adrenoleukodystrophy revealed a severe degeneration of the white matter involving both hemispheres of cerebrum and cerebellum, while the axons were preserved [57].”

What the sources say

• Not checked yetcites [57] Aubourg P Scotto J Rocchiccioli F Feldmann-Pautrat D Robain O Neonatal adrenoleukodystrophy J Neurol Neurosurg Psychiatry 1986 49 77 86 2420940 PMC1028652 source

In the paper

“Surprisingly, in patients suffering from acatalasemia, an inherited peroxisomal disorder caused by the loss of functional catalase, no neurological involvement or brain abnormalities have been described, although this enzyme plays such a prominent role in oxygen metabolism [37,38].”

What the sources say

• Not checked yetcites [37] van der Knaap MS Valk J The MR spectrum of peroxisomal disorders Neuroradiology 1991 33 30 37 2027442 source
• Not checked yetcites [38] Eaton JW Ma M Acatalasemia Scriver CR Beaudet AL Sly WS Valle D The Metabolic and Molecular Bases of Inherited Disease McGraw-Hill New York 1995 2371 2383

In the paper

“Prolonged hyperactivity of peroxisomes has also been linked to the overproduction of H2O2 in the liver of acyl-CoA oxidase-deficient mice [36].”

What the sources say

• Not checked yetcites [36] Fan CY Pan J Usuda N Yeldandi AV Rao MS Reddy JK Steatohepatitis, spontaneous peroxisome proliferation and liver tumors in mice lacking peroxisomal fatty acyl-CoA oxidase. Implications for peroxisome proliferator-activated receptor alpha natural ligand metabolism J Biol Chem 1998 273 15639 15645 9624157 source

In the paper

“In patients with Zellweger syndrome, the most prominent feature of the brain pathology is a malformation of the cortex, which has been attributed to neuronal migration defects.”

What the sources say

• Not checked yetcites [49] Volpe JJ Adams RD Cerebro-hepato-renal syndrome of Zellweger: an inherited disorder of neuronal migration Acta Neuropathol 1972 20 175 198 5043999 source
• Not checked yetcites [50] Evrard P Caviness VS Jr Prats-Vinas J Lyon G The mechanism of arrest of neuronal migration in the Zellweger malformation: an hypothesis bases upon cytoarchitectonic analysis Acta Neuropathol 1978 41 109 117 636841 source

In the paper

“In addition to these migration defects, within their first year of life, all patients with Zellweger syndrome display white matter abnormalities in the CNS, which have been observed by histological analyses and brain magnetic resonance tomography (MRT) studies [52–55].”

What the sources say

• Not checked yetcites [52] Powers JM The pathology of peroxisomal disorders with pathogenetic considerations J Neuropathol Exp Neurol 1995 54 710 719 7666061 source
• Not checked yetcites [53] Weller S Rosewich H Gartner J Cerebral MRI as a valuable diagnostic tool in Zellweger spectrum patients J Inherit Metab Dis 2008 31 270 280 18415699 source
• Not checked yetcites [54] Poll-The BT Gartner J Clinical diagnosis, biochemical findings and MRI spectrum of peroxisomal disorders Biochim Biophys Acta 2012 1822 1421 1429 22483868 source
• Not checked yetcites [55] Barkovich AJ Peck WW MR of Zellweger syndrome AJNR Am J Neuroradiol 1997 18 1163 1170 9194444 PMC8337298

In the paper

“However, a genotype-phenotype correlation has been described for PEX gene mutations [45].”

What the sources say

• Not checked yetcites [45] Steinberg SJ Dodt G Raymond GV Braverman NE Moser AB Moser HW Peroxisome biogenesis disorders Biochim Biophys Acta 2006 1763 1733 1748 17055079 source

In the paper

“The nature and location of the mutations determine whether the mutated peroxin can still contribute to the import machinery and allows residual metabolic functions of the peroxisomes in these patients.”

In the paper

“The identification of PBD complementation groups and their genetic basis has revealed that there are no clear boundaries between Zellweger syndrome, neonatal adrenoleukodystrophy and infantile Refsum disease, as they can all be caused by mutations in the same gene.”

What the sources say

• Not checked yetcites [45] Steinberg SJ Dodt G Raymond GV Braverman NE Moser AB Moser HW Peroxisome biogenesis disorders Biochim Biophys Acta 2006 1763 1733 1748 17055079 source

In the paper

“Because myelination is still ongoing during this early period, it cannot be clearly established, whether the lack of peroxisomal functions causes abnormal myelination, early demyelination or both processes simultaneously [56].”

What the sources say

• Not checked yetcites [56] Baes M Aubourg P Peroxisomes, myelination, and axonal integrity in the CNS Neuroscientist 2009 15 367 379 19666893 source

In the paper

“In accordance, also the neurological manifestations vary from primarily neurodevelopmental alterations in the most severe phenotypes to mainly degenerative abnormalities in the milder cases [48].”

What the sources say

• Not checked yetcites [48] Barth PG Majoie CB Gootjes J Wanders RJ Waterham HR van der Knaap MS de Klerk JB Smeitink J Poll-The BT Neuroimaging of peroxisome biogenesis disorders (Zellweger spectrum) with prolonged survival Neurology 2004 62 439 444 14872027 source

In the paper

“These findings indicate that the level of peroxisome-related metabolites in plasma may not necessarily reflect the level of accumulation in tissues.”

In the paper

“When the Pex2 mutation was maintained on a mixed genetic background (Swiss Webster × 129Svev), about 25% of the Pex2−/− pups survived for one to two weeks [66].”

What the sources say

• Not checked yetcites [66] Faust PL Su HM Moser A Moser HW The peroxisome deficient PEX2 Zellweger mouse: pathologic and biochemical correlates of lipid dysfunction J Mol Neurosci 2001 16 289 297 discussion 317-221 11478384 source

In the paper

“This implies that, based on plasma metabolites linked to peroxisomal function, some of these patients would have escaped the diagnosis of a Zellweger spectrum disorder.”

In the paper

“Whereas PEX11α appears not to be essential for the formation of functional peroxisomes”

In the paper

“Furthermore, postnatal survival could be improved by oral bile acid application (9% alive after 30 days) [67].”

What the sources say

• Not checked yetcites [67] Keane MH Overmars H Wikander TM Ferdinandusse S Duran M Wanders RJ Faust PL Bile acid treatment alters hepatic disease and bile acid transport in peroxisome-deficient PEX2 Zellweger mice Hepatology 2007 45 982 997 17393522 source

In the paper

“Currently, several mouse models of the Zellweger spectrum disorders are available, which are represented by mice with targeted deletions in the genes encoding the peroxins PEX2, PEX5 or PEX13 [60–62].”

What the sources say

• Not checked yetcites [60] Baes M Gressens P Baumgart E Carmeliet P Casteels M Fransen M Evrard P Fahimi D Declercq PE Collen D van Veldhoven PP A mouse model for Zellweger syndrome Nat Genet 1997 17 49 57 9288097 source
• Not checked yetcites [61] Faust PL Hatten ME Targeted deletion of the PEX2 peroxisome assembly gene in mice provides a model for Zellweger syndrome, a human neuronal migration disorder J Cell Biol 1997 139 1293 1305 9382874 PMC2140200 source
• Not checked yetcites [62] Maxwell M Bjorkman J Nguyen T Sharp P Finnie J Paterson C Tonks I Paton BC Kay GF Crane DI Pex13 inactivation in the mouse disrupts peroxisome biogenesis and leads to a Zellweger syndrome phenotype Mol Cell Biol 2003 23 5947 5957 12897163 PMC166343 source

In the paper

“These studies revealed multiple anomalies affecting the interaction of climbing fibers, granule cells and Purkinje cells and, thus, the cerebellar circuitry.”

What the sources say

• Not checked yetcites [68] Faust PL Abnormal cerebellar histogenesis in PEX2 Zellweger mice reflects multiple neuronal defects induced by peroxisome deficiency J Comp Neurol 2003 461 394 413 12746876 source
• Not checked yetcites [69] Faust PL Banka D Siriratsivawong R Ng VG Wikander TM Peroxisome biogenesis disorders: the role of peroxisomes and metabolic dysfunction in developing brain J Inherit Metab Dis 2005 28 369 383 15868469 source

In the paper

“Recently also a knock-in mouse model carrying a missense mutation in the Pex1 gene (Pex1-G844D) was reported, which recapitulates the most frequent mutation in the human Zellweger spectrum disorders with a milder pathology [63].”

What the sources say

• Not checked yetcites [63] Hiebler S Masuda T Hacia JG Moser AB Faust PL Liu A Chowdhury N Huang N Lauer A Bennett J Watkins PA The Pex1-G844D mouse: a model for mild human Zellweger spectrum disorder Mol Genet Metab 2014 111 522 532 24503136 PMC4901203 source

In the paper

“These Nestin-Pex5−/− mice appear normal at birth, but develop substantial growth retardation after the first postnatal week.”

What the sources say

• Not checked yetcites [71] Hulshagen L Krysko O Bottelbergs A Huyghe S Klein R Van Veldhoven PP De Deyn PP D’Hooge R Hartmann D Baes M Absence of functional peroxisomes from mouse CNS causes dysmyelination and axon degeneration J Neurosci 2008 28 4015 4027 18400901 PMC6670456 source

In the paper

“With regard to the Pex11-related mouse models, it should be noted that in contrast to the other peroxins, the PEX11 family members act as membrane elongation factors during peroxisome proliferation [70].”

What the sources say

• Not checked yetcites [70] Koch J Pranjic K Huber A Ellinger A Hartig A Kragler F Brocard C PEX11 family members are membrane elongation factors that coordinate peroxisome proliferation and maintenance J Cell Sci 2010 123 3389 3400 20826455 source

In the paper

“The predominant neurological symptom in the adult patients was a gait disorder, caused by different combinations of cerebellar syndrome, pyramidal tract dysfunction and peripheral neuropathy.”

What the sources say

• Not checked yetcites [47] Berendse K Engelen M Ferdinandusse S Majoie CB Waterham HR Vaz FM Koelman JH Barth PG Wanders RJ Poll-The BT Zellweger spectrum disorders: clinical manifestations in patients surviving into adulthood J Inherit Metab Dis 2015 PMC4710674 26287655

In the paper

“This results in the ablation of peroxisomal functions in the vast majority of neurons, astrocytes and oligodendrocytes of mice already at prenatal stages [71].”

What the sources say

• Not checked yetcites [71] Hulshagen L Krysko O Bottelbergs A Huyghe S Klein R Van Veldhoven PP De Deyn PP D’Hooge R Hartmann D Baes M Absence of functional peroxisomes from mouse CNS causes dysmyelination and axon degeneration J Neurosci 2008 28 4015 4027 18400901 PMC6670456 source

In the paper

“The Purkinje cells displayed stunted dendrite trees with abnormal branches and spine morphology.”

What the sources say

• Not checked yetcites [68] Faust PL Abnormal cerebellar histogenesis in PEX2 Zellweger mice reflects multiple neuronal defects induced by peroxisome deficiency J Comp Neurol 2003 461 394 413 12746876 source
• Not checked yetcites [69] Faust PL Banka D Siriratsivawong R Ng VG Wikander TM Peroxisome biogenesis disorders: the role of peroxisomes and metabolic dysfunction in developing brain J Inherit Metab Dis 2005 28 369 383 15868469 source

In the paper

“In addition, progressive axonal swellings along Purkinje cell axons indicated ongoing dystrophic, neurodegenerative processes.”

What the sources say

• Not checked yetcites [68] Faust PL Abnormal cerebellar histogenesis in PEX2 Zellweger mice reflects multiple neuronal defects induced by peroxisome deficiency J Comp Neurol 2003 461 394 413 12746876 source
• Not checked yetcites [69] Faust PL Banka D Siriratsivawong R Ng VG Wikander TM Peroxisome biogenesis disorders: the role of peroxisomes and metabolic dysfunction in developing brain J Inherit Metab Dis 2005 28 369 383 15868469 source

In the paper

“The disturbed dendritic spine compartmentalization reflected a delayed arborization and translocation of the climbing fibers from the inferior olivary nucleus (the major excitatory input to the Purkinje cells from the caudal medulla).”

What the sources say

• Not checked yetcites [68] Faust PL Abnormal cerebellar histogenesis in PEX2 Zellweger mice reflects multiple neuronal defects induced by peroxisome deficiency J Comp Neurol 2003 461 394 413 12746876 source
• Not checked yetcites [69] Faust PL Banka D Siriratsivawong R Ng VG Wikander TM Peroxisome biogenesis disorders: the role of peroxisomes and metabolic dysfunction in developing brain J Inherit Metab Dis 2005 28 369 383 15868469 source

In the paper

“the absence of PEX11β leads to several pathological features shared by the mouse models of Zellweger syndrome, including neuronal migration defects, enhanced neuronal apoptosis, developmental delay, hypotonia and neonatal lethality [65].”

What the sources say

• Not checked yetcites [65] Li X Baumgart E Morrell JC Jimenez-Sanchez G Valle D Gould SJ PEX11 beta deficiency is lethal and impairs neuronal migration but does not abrogate peroxisome function Mol Cell Biol 2002 22 4358 4365 12024045 PMC133847 source

In the paper

“Also cerebellar malformation was explored in all three models of PBD revealing abnormalities in cerebellar foliation.”

In the paper

“Accordingly, pristanic acid and the bile acid intermediates DHCA and THCA, but not VLCFA, accumulate in AMACR-deficient patients (Fig. 1) [93].”

What the sources say

• Not checked yetcites [93] Ferdinandusse S Denis S Clayton PT Graham A Rees JE Allen JT McLean BN Brown AY Vreken P Waterham HR Wanders RJ Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy Nat Genet 2000 24 188 191 10655068 source

In the paper

“Taken together, these studies indicate that in the murine brain, peroxisomes are most crucial for oligodendrocytes and the myelin compartment.”

In the paper

“Most patients show neonatal onset of hypotonia, seizures, failure to thrive, hepatomegaly, psychomotor retardation, sensory deafness, absent reflexes, and visual loss with retinopathy and extinguished electroretinograms [80].”

What the sources say

• Not checked yetcites [80] Wanders RJ Poll-The BT Role of peroxisomes in human lipid metabolism and its importance for neurological development Neurosci Lett 2015 26095698 source

In the paper

“This finding is further corroborated by observations in Pex5-deficient mice (ubiquitous KO), in which liver-specific ectopic expression of Pex5 [77] resulted in partial rescue of the brain defects.”

What the sources say

• Not checked yetcites [77] Janssen A Gressens P Grabenbauer M Baumgart E Schad A Vanhorebeek I Brouwers A Declercq PE Fahimi D Evrard P Schoonjans L Neuronal migration depends on intact peroxisomal function in brain and in extraneuronal tissues J Neurosci 2003 23 9732 9741 14586000 PMC6740889 source

In the paper

“The mechanisms are not resolved but Faust and collaborators showed that bile acid treatment can partially restore the cerebellar anomalies in Pex2-deficient mice [69].”

What the sources say

• Not checked yetcites [69] Faust PL Banka D Siriratsivawong R Ng VG Wikander TM Peroxisome biogenesis disorders: the role of peroxisomes and metabolic dysfunction in developing brain J Inherit Metab Dis 2005 28 369 383 15868469 source

In the paper

“The severe form of DBP deficiency mimics Zellweger syndrome in all aspects including cranio-facial dysmorphism, neuronal migration defects (similar to that depicted in Fig. 2A) and premature death [84].”

What the sources say

• Not checked yetcites [84] Ferdinandusse S Ylianttila MS Gloerich J Koski MK Oostheim W Waterham HR Hiltunen JK Wanders RJ Glumoff T Mutational spectrum of D-bifunctional protein deficiency and structure-based genotype–phenotype analysis Am J Hum Genet 2006 78 112 124 16385454 PMC1380208 source

In the paper

“However, the absence of developmental problems in the CNS of racemase-deficient mice, in which bile acid precursors accumulate as well [78], renders an exclusive effect of bile acid precursors quite unlikely.”

What the sources say

• Not checked yetcites [78] Savolainen K Kotti TJ Schmitz W Savolainen TI Sormunen RT Ilves M Vainio SJ Conzelmann E Hiltunen JK A mouse model for alpha-methylacyl-CoA racemase deficiency: adjustment of bile acid synthesis and intolerance to dietary methyl-branched lipids Hum Mol Genet 2004 13 955 965 15016763 source

In the paper

“In contrast, peroxisome ablation in projection neurons of neocortex and hippocampus, obtained with Nex-Cre driver mice [76], or in astrocytes obtained with GFAP-Cre drivers [76], had no obvious deleterious effect on brain development or function.”

What the sources say

• Not checked yetcites [76] Bottelbergs A Verheijden S Hulshagen L Gutmann DH Goebbels S Nave KA Kassmann C Baes M Axonal integrity in the absence of functional peroxisomes from projection neurons and astrocytes Glia 2010 58 1532 1543 20578053 source

In the paper

“However, upon phytol supplementation of the diet, the mice developed severe pathology in the brain after 40 days, including demyelination and activation of astroglial cells [101].”

What the sources say

• Not checked yetcites [101] Selkala EM Nair RR Schmitz W Kvist AP Baes M Hiltunen JK Autio KJ Phytol is lethal for Amacr-deficient mice Biochim Biophys Acta 2015 1851 1394 1405 26248199 source

In the paper

“Progressive motor impairments ensue, resulting in lethargy and death before six months of age.”

What the sources say

• Not checked yetcites [71] Hulshagen L Krysko O Bottelbergs A Huyghe S Klein R Van Veldhoven PP De Deyn PP D’Hooge R Hartmann D Baes M Absence of functional peroxisomes from mouse CNS causes dysmyelination and axon degeneration J Neurosci 2008 28 4015 4027 18400901 PMC6670456 source

In the paper

“These studies indicate a role of brain-extrinsic effects (effects originating from outside the brain) in CNS development in peroxisomal disorders.”

In the paper

“Similarly, selective knockout (KO) of Pex5 in oligodendrocytes by using Cnp-Cre drivers had severe consequences for the adult brain [75].”

What the sources say

• Not checked yetcites [75] Kassmann CM Lappe-Siefke C Baes M Brugger B Mildner A Werner HB Natt O Michaelis T Prinz M Frahm J Nave KA Axonal loss and neuroinflammation caused by peroxisome-deficient oligodendrocytes Nat Genet 2007 39 969 976 17643102 source

In the paper

“However, only for SCPx, the thiolase required for the breakdown of branched-chain fatty acids, a single patient with a deficiency of the enzyme (MIM #613724) has been described so far [102].”

What the sources say

• Not checked yetcites [102] Ferdinandusse S Kostopoulos P Denis S Rusch H Overmars H Dillmann U Reith W Haas D Wanders RJ Duran M Marziniak M Mutations in the gene encoding peroxisomal sterol carrier protein X (SCPx) cause leukencephalopathy with dystonia and motor neuropathy Am J Hum Genet 2006 78 1046 1052 16685654 PMC1474093 source

In the paper

“postnatally, delayed cerebellar development including immature foliation and dendritic arborization of Purkinje cells [72].”

What the sources say

• Not checked yetcites [72] Krysko O Hulshagen L Janssen A Schutz G Klein R De Bruycker M Espeel M Gressens P Baes M Neocortical and cerebellar developmental abnormalities in conditions of selective elimination of peroxisomes from brain or from liver J Neurosci Res 2007 85 58 72 17075904 source

In the paper

“Thus, in contrast to the human disorders, where Zellweger syndrome and DBP deficiency are clinically very similar, their respective mouse models are remarkably different.”

In the paper

“In the developing brain, a defect in neuronal layer formation in the cerebral cortex was observed indicative of neuronal migration defects”

What the sources say

• Not checked yetcites [72] Krysko O Hulshagen L Janssen A Schutz G Klein R De Bruycker M Espeel M Gressens P Baes M Neocortical and cerebellar developmental abnormalities in conditions of selective elimination of peroxisomes from brain or from liver J Neurosci Res 2007 85 58 72 17075904 source

In the paper

“As peroxisomes fulfill a variety of metabolic functions, which are concomitantly ablated upon inactivation of peroxisome biogenesis (in human patients suffering from Zellweger syndrome or in Pex-deficient mice), the attribution of particular aspects of brain pathology cannot be traced back to a single pathway such as β-oxidation.”

In the paper

“However, also the selective loss of peroxisomal functions in hepatocytes of the liver, obtained by α-fetoprotein-Cre driver mice [72], results in brain abnormalities including defects in cerebral neuronal migration and cerebellar development (hypotrophy, increased apoptosis, immature foliation, delayed granule cell migration and stunted Purkinje cells).”

What the sources say

• Not checked yetcites [72] Krysko O Hulshagen L Janssen A Schutz G Klein R De Bruycker M Espeel M Gressens P Baes M Neocortical and cerebellar developmental abnormalities in conditions of selective elimination of peroxisomes from brain or from liver J Neurosci Res 2007 85 58 72 17075904 source

In the paper

“Still, in many respects, the clinical presentation of acyl-CoA oxidase deficiency (formerly pseudoneonatal adrenoleukodystrophy) resembles Zellweger spectrum disorders, notably neonatal adrenoleukodystrophy [79].”

What the sources say

• Not checked yetcites [79] Ferdinandusse S Denis S Hogenhout EM Koster J van Roermund CW Moser Wanders RJ Waterham HR Clinical, biochemical, and mutational spectrum of peroxisomal acyl-coenzyme A oxidase deficiency Hum Mutat 2007 28 904 912 17458872 source

In the paper

“This further demonstrates that peroxisome-related neurological deficits and the level of metabolites linked to peroxisomal functions do not necessarily correlate when measured in the blood of patients.”

In the paper

“Due to the fact that not only ether lipid biosynthesis but also peroxisomal α-oxidation is impaired in RCDP type 1, it is classified as a PBD rather than a pure ether lipid biosynthesis defect (see also Section 5.1).”

In the paper

“the disease in patients with mutations specifically affecting the long isoform of PEX5, PEX5L, which is required for efficient transport of cargo-loaded PEX7 to peroxisomes [184], was designated RCDP type 5 [185].”

What the sources say

• Not checked yetcites [184] Kunze M Malkani N Maurer-Stroh S Wiesinger C Schmid JA Berger J Mechanistic insights into PTS2-mediated peroxisomal protein import: the co-receptor PEX5L drastically increases the interaction strength between the cargo protein and the receptor PEX7 J Biol Chem 2015 290 4928 4940 25538232 PMC4335231 source
• Not checked yetcites [185] Baroy T Koster J Stromme P Ebberink MS Misceo D Ferdinandusse S Holmgren A Hughes T Merckoll E Westvik J Woldseth B A novel type of rhizomelic chondrodysplasia punctata, RCDP5, is caused by loss of the PEX5 long isoform Hum Mol Genet 2015 24 5845 5854 26220973 source

In the paper

“Human ABCD1 transports CoA-activated saturated straight-chain VLCFA across the peroxisomal membrane for further degradation by the peroxisomal β-oxidation machinery (Fig. 1) [111].”

What the sources say

• Not checked yetcites [111] Wiesinger C Kunze M Regelsberger G Forss-Petter S Berger J Impaired very long-chain acyl-CoA beta-oxidation in human X-linked adrenoleukodystrophy fibroblasts is a direct consequence of ABCD1 transporter dysfunction J Biol Chem 2013 288 19269 19279 23671276 PMC3696697 source

In the paper

“Allogenic hematopoietic stem cell transplantation [145,146] and autologous stem cell-based gene therapy [147] can arrest the inflammatory demyelinating process with a typical delay of 12–18 months, which has been attributed to the slow replacement of microglia with bone marrow-derived phagocytes [147,148].”

What the sources say

• Not checked yetcites [145] Peters C Charnas LR Tan Y Ziegler RS Shapiro EG DeFor T Grewal SS Orchard PJ Abel SL Goldman AI Ramsay NK Cerebral X-linked adrenoleukodystrophy: the international hematopoietic cell transplantation experience from 1982 to 1999 Blood 2004 104 881 888 15073029 source
• Not checked yetcites [146] Aubourg P Blanche S Jambaque I Rocchiccioli F Kalifa G Naud-Saudreau C Rolland MO Debre M Chaussain JL Griscelli C Reversal of early neurologic and neuroradiologic manifestations of X-linked adrenoleukodystrophy by bone marrow transplantation New Engl J Med 1990 322 1860 1866 2348839 source
• Not checked yetcites [147] Cartier N Hacein-Bey-Abina S Bartholomae CC Veres G Schmidt M Kutschera I Vidaud M Abel U Dal-Cortivo L Caccavelli L Mahlaoui N Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy Science 2009 326 818 823 19892975 source

In the paper

“The most severe form of the disease leads to lethality within the first years of life, often due to respiratory failure.”

What the sources say

• Not checked yetcites [192] White AL Modaff P Holland-Morris F Pauli RM Natural history of rhizomelic chondrodysplasia punctata Am J Med Genet A 2003 118A 332 342 12687664 source
• Not checked yetcites [193] Motley AM Brites P Gerez L Hogenhout E Haasjes J Benne R Tabak HF Wanders RJ Waterham HR Mutational spectrum in the PEX7 gene and functional analysis of mutant alleles in 78 patients with rhizomelic chondrodysplasia punctata type 1 Am J Hum Genet 2002 70 612 624 11781871 PMC384941 source
• Not checked yetcites [194] Poll-The BT Maroteaux P Narcy C Quetin P Guesnu M Wanders RJ Schutgens RB Saudubray JM A new type of chondrodysplasia punctata associated with peroxisomal dysfunction J Inherit Metab Dis 1991 14 361 363 1770792 source

In the paper

“The pathology in all subtypes of RCDP has been more or less exclusively assigned to the lack of plasmalogens”

What the sources say

• Not checked yetcites [186] Hoefler G Hoefler S Watkins PA Chen WW Moser A Baldwin V McGillivary B Charrow J Friedman JM Rutledge L Biochemical abnormalities in rhizomelic chondrodysplasia punctata J Pediatr 1988 112 726 733 2452243 source

In the paper

“Inherited defects in the ABCD1 (formerly ALD) gene are the genetic basis for X-linked adrenoleukodystrophy (X-ALD; MIM #300100) [108].”

What the sources say

• Not checked yetcites [108] Mosser J Douar AM Sarde CO Kioschis P Feil R Moser H Poustka AM Mandel JL Aubourg P Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters Nature 1993 361 726 730 8441467 source

In the paper

“Recently, two additional subtypes of RCDP were identified based on the strong reduction of plasmalogen levels in the patients and the similarity of their symptoms with “classical” RCDP.”

What the sources say

• Not checked yetcites [80] Wanders RJ Poll-The BT Role of peroxisomes in human lipid metabolism and its importance for neurological development Neurosci Lett 2015 26095698 source
• Not checked yetcites [185] Baroy T Koster J Stromme P Ebberink MS Misceo D Ferdinandusse S Holmgren A Hughes T Merckoll E Westvik J Woldseth B A novel type of rhizomelic chondrodysplasia punctata, RCDP5, is caused by loss of the PEX5 long isoform Hum Mol Genet 2015 24 5845 5854 26220973 source

In the paper

“Irrespective of the affected gene, all RCDP patients share common symptoms.”

What the sources say

• Not checked yetcites [187] Braverman NE Moser AB Functions of plasmalogen lipids in health and disease Biochim Biophys Acta 2012 1822 1442 1452 22627108 source

In the paper

“The severity of the disease varies remarkably, depending strongly on the residual activity of the affected enzyme and, thus, the level of plasmalogens [188–191].”

What the sources say

• Not checked yetcites [188] Noguchi M Honsho M Abe Y Toyama R Niwa H Sato Y Ghaedi K Rahmanifar A Shafeghati Y Fujiki Y Mild reduction of plasmalogens causes rhizomelic chondrodysplasia punctata: functional characterization of a novel mutation J Hum Genet 2014 59 387 392 24849933 source
• Not checked yetcites [189] Nuoffer JM Pfammatter JP Spahr A Toplak H Wanders RJ Schutgens RB Wiesmann UN Chondrodysplasia punctata with a mild clinical course J Inherit Metab Dis 1994 17 60 66 7914249 source
• Not checked yetcites [190] Braverman N Chen L Lin P Obie C Steel G Douglas P Chakraborty PK Clarke JT Boneh A Moser A Moser H Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype Hum Mutat 2002 20 284 297 12325024 source
• Not checked yetcites [191] Bams-Mengerink AM Koelman JH Waterham H Barth PG Poll-The BT The neurology of rhizomelic chondrodysplasia punctata Orphanet J Rare Dis 2013 8 174 24172221 PMC4228450 source

In the paper

“In the human brain, based on immunohistochemical detection, ABCD1 is predominantly expressed in oligodendrocytes, microglia, astrocytes and endothelial cells but not in most neurons, with the exception of a few regions: hypothalamus, basal nucleus of Meynert, periaqueductal gray matter and the locus coeruleus [16,30].”

What the sources say

• Not checked yetcites [16] Fouquet F Zhou JM Ralston E Murray K Troalen F Magal E Robain O Dubois-Dalcq M Aubourg P Expression of the adrenoleukodystrophy protein in the human and mouse central nervous system Neurobiol Dis 1997 3 271 285 9173925 source
• Not checked yetcites [30] Hoftberger R Kunze M Weinhofer I Aboul-Enein F Voigtlander T Oezen I Amann G Bernheimer H Budka H Berger J Distribution and cellular localization of adrenoleukodystrophy protein in human tissues: implications for X-linked adrenoleukodystrophy Neurobiol Dis 2007 28 165 174 17761426 source

In the paper

“the disorder of three patients with a deficiency in FAR1, the gene coding for fatty acyl-CoA reductase 1, which generates the fatty alcohols necessary to form the ether bond of the 1-alkyl chain in ether phospholipid biosynthesis [183], was categorized as RCDP type 4 [80].”

What the sources say

• Not checked yetcites [183] Buchert R Tawamie H Smith C Uebe S Innes AM Al Hallak B Ekici AB Sticht H Schwarze B Lamont RE Parboosingh JS A peroxisomal disorder of severe intellectual disability, epilepsy, and cataracts due to fatty acyl-CoA reductase 1 deficiency Am J Hum Genet 2014 95 602 610 25439727 PMC4225589 source
• Not checked yetcites [80] Wanders RJ Poll-The BT Role of peroxisomes in human lipid metabolism and its importance for neurological development Neurosci Lett 2015 26095698 source

In the paper

“also other ether phospholipids, like alkylphospholipids (lacking the vinyl ether bond characteristic for plasmalogens) or platelet-activating factor, are depleted in all types of RCDP”

What the sources say

• Not checked yetcites [186] Hoefler G Hoefler S Watkins PA Chen WW Moser A Baldwin V McGillivary B Charrow J Friedman JM Rutledge L Biochemical abnormalities in rhizomelic chondrodysplasia punctata J Pediatr 1988 112 726 733 2452243 source

In the paper

“However, this hypothesis is strongly weakened by the presence of cerebellar atrophy in a case of RCDP type 3, in which ether lipid deficiency is the only metabolic defect, and, conversely, by the absence of cerebellar atrophy in a case with particularly high phytanic acid levels [191].”

What the sources say

• Not checked yetcites [191] Bams-Mengerink AM Koelman JH Waterham H Barth PG Poll-The BT The neurology of rhizomelic chondrodysplasia punctata Orphanet J Rare Dis 2013 8 174 24172221 PMC4228450 source

In the paper

“These findings emphasize the fact that multiple peroxisomal functions are required for proper development of the brain.”

In the paper

“Furthermore, in murine cell lines, plasmalogens seem to counteract neuronal death elicited by serum starvation [223,224] by utilizing a process, which has been reported to involve protein kinase B (AKT) signaling [224].”

What the sources say

• Not checked yetcites [223] Yamashita S Kanno S Nakagawa K Kinoshita M Miyazawa T Extrinsic plasmalogens suppress neuronal apoptosis in mouse neuroblastoma Neuro-2A cells: importance of plasmalogen molecular species RSC Adv 2015 5 61012 61020 source
• Not checked yetcites [224] Hossain MS Ifuku M Take S Kawamura J Miake K Katafuchi T Plasmalogens rescue neuronal cell death through an activation of AKT and ERK survival signaling PLoS One 2013 8 e83508 24376709 PMC3869814 source

In the paper

“This concept is also supported by the finding that plasmalogens suppress microglia activation after systemic injection of lipopolysaccharides (LPS) in mice [221,222].”

What the sources say

• Not checked yetcites [221] Ifuku M Katafuchi T Mawatari S Noda M Miake K Sugiyama M Fujino T Anti-inflammatory/anti-amyloidogenic effects of plasmalogens in lipopolysaccharide-induced neuroinflammation in adult mice J Neuroinflammation 2012 9 197 22889165 PMC3444880 source
• Not checked yetcites [222] Katafuchi T Ifuku M Mawatari S Noda M Miake K Sugiyama M Fujino T Effects of plasmalogens on systemic lipopolysaccharide-induced glial activation and beta-amyloid accumulation in adult mice Ann N Y Acad Sci 2012 1262 85 92 22823439 source

In the paper

“The age of onset of seizure activity is reportedly higher in milder cases of RCDP [191].”

What the sources say

• Not checked yetcites [191] Bams-Mengerink AM Koelman JH Waterham H Barth PG Poll-The BT The neurology of rhizomelic chondrodysplasia punctata Orphanet J Rare Dis 2013 8 174 24172221 PMC4228450 source

In the paper

“Furthermore, hypomyelination in cerebellum (and also in cortical areas) of Gnpat KO mice was accompanied by changes in the architecture of the nodes of Ranvier resulting in a delay in the propagation of action potentials [218].”

What the sources say

• Not checked yetcites [218] Teigler A Komljenovic D Draguhn A Gorgas K Just WW Defects in myelination, paranode organization and Purkinje cell innervation in the ether lipid-deficient mouse cerebellum Hum Mol Genet 2009 18 1897 1908 19270340 PMC2722228 source

In the paper

“Furthermore, hypomorphic mouse models with residual transcript levels of the Pex7 [215] or the Agps [216] gene and, consequently, residual levels of ether lipids have been described, which mimic the milder form of the human disease.”

What the sources say

• Not checked yetcites [215] Braverman N Zhang R Chen L Nimmo G Scheper S Tran T Chaudhury R Moser A Steinberg S A Pex7 hypomorphic mouse model for plasmalogen deficiency affecting the lens and skeleton Mol Genet Metab 2010 99 408 416 20060764 PMC2839039 source
• Not checked yetcites [216] Liegel R Chang B Dubielzig R Sidjanin DJ Blind sterile 2 (bs2), a hypomorphic mutation in Agps, results in cataracts and male sterility in mice Mol Genet Metab 2011 103 51 59 21353609 PMC3081956 source

In the paper

“Concordantly, foliation defects with underdevelopment of fissures, particularly affecting foliae VI and VII, have been reported in Gnpat KO mice at different postnatal stages [218,225].”

What the sources say

• Not checked yetcites [218] Teigler A Komljenovic D Draguhn A Gorgas K Just WW Defects in myelination, paranode organization and Purkinje cell innervation in the ether lipid-deficient mouse cerebellum Hum Mol Genet 2009 18 1897 1908 19270340 PMC2722228 source
• Not checked yetcites [225] Krysko O Bottelbergs A Van Veldhoven P Baes M Combined deficiency of peroxisomal beta-oxidation and ether lipid synthesis in mice causes only minor cortical neuronal migration defects but severe hypotonia Mol Genet Metab 2010 100 71 76 20202875 source

In the paper

“Frequent delay in brain development is further reflected by the finding of microcephaly in many RCDP cases.”

In the paper

“The severe form of the disease is usually accompanied by progressive cerebellar atrophy [195], which is caused by a pronounced loss of Purkinje cells and, to a lesser extent, other cell types in the cerebellum [202].”

What the sources say

• Not checked yetcites [195] Bams-Mengerink AM Majoie CB Duran M Wanders RJ Van Hove J Scheurer CD Barth PG Poll-The BT MRI of the brain and cervical spinal cord in rhizomelic chondrodysplasia punctata Neurology 2006 66 798 803 discussion 789 16567694 source
• Not checked yetcites [202] Powers JM Kenjarski TP Moser AB Moser HW Cerebellar atrophy in chronic rhizomelic chondrodysplasia punctata: a potential role for phytanic acid and calcium in the death of its Purkinje cells Acta Neuropathol 1999 98 129 134 10442551 source

In the paper

“In line with myelination defects also in the PNS, peripheral neuropathy has been reported in a clinical subset of RCDP patients [201].”

What the sources say

• Not checked yetcites [201] van den Brink DM Brites P Haasjes J Wierzbicki AS Mitchell J Lambert-Hamill M de Belleroche J Jansen GA Waterham HR Wanders RJ Identification of PEX7 as the second gene involved in Refsum disease Am J Hum Genet 2003 72 471 477 12522768 PMC379239 source

In the paper

“Thus, in addition to peroxisomal β-oxidation, also ether lipid biosynthesis appears to be crucial for cerebellar development and function.”

In the paper

“In addition to the brain pathology, patients suffering from the severe form of RCDP often develop stenosis of the spinal canal (cervical stenosis) [195,207].”

What the sources say

• Not checked yetcites [195] Bams-Mengerink AM Majoie CB Duran M Wanders RJ Van Hove J Scheurer CD Barth PG Poll-The BT MRI of the brain and cervical spinal cord in rhizomelic chondrodysplasia punctata Neurology 2006 66 798 803 discussion 789 16567694 source
• Not checked yetcites [207] Khanna AJ Braverman NE Valle D Sponseller PD Cervical stenosis secondary to rhizomelic chondrodysplasia punctata Am J Med Genet 2001 99 63 66 11170096 source

In the paper

“Plasmalogen-deficient myelin might be more prone to oxidative damage [231]; however, this idea is weakened by the observations of reduced rather than elevated levels of malondialdehyde and no substantial change in other oxidative stress markers in the brains of ether lipid-deficient mice [40,73].”

What the sources say

• Not checked yetcites [231] Luoma AM Kuo F Cakici O Crowther MN Denninger AR Avila RL Brites P Kirschner DA Plasmalogen phospholipids protect internodal myelin from oxidative damage Free Radic Biol Med 2015 84 296 310 25801291 source
• Not checked yetcites [40] Brodde A Teigler A Brugger B Lehmann WD Wieland F Berger J Just WW Impaired neurotransmission in ether lipid-deficient nerve terminals Hum Mol Genet 2012 21 2713 2724 22403185 PMC4880048 source
• Not checked yetcites [73] Bottelbergs A Verheijden S Van Veldhoven PP Just W Devos R Baes M Peroxisome deficiency but not the defect in ether lipid synthesis causes activation of the innate immune system and axonal loss in the central nervous system J Neuroinflammation 2012 9 61 22458306 PMC3419640 source

In the paper

“Lens anomalies, particularly bilateral cataracts, have been reported in all ether lipid-deficient mouse models, including the hypomorphic mice.”

In the paper

“Studies in synaptosomes isolated from cortex, mimicking the process of synaptic transmission, have revealed a decrease in calcium-dependent release of the neurotransmitters glutamate and acetylcholine in Gnpat KO mice [40].”

What the sources say

• Not checked yetcites [40] Brodde A Teigler A Brugger B Lehmann WD Wieland F Berger J Just WW Impaired neurotransmission in ether lipid-deficient nerve terminals Hum Mol Genet 2012 21 2713 2724 22403185 PMC4880048 source

In the paper

“In the first description of the Pex7 KO mouse, neuronal migration defects in the neocortex of mutant embryos were reported; however, these were much less pronounced than the migration deficits in mice completely lacking peroxisomes (e.g. Pex5 KO mice) [210].”

What the sources say

• Not checked yetcites [210] Brites P Motley AM Gressens P Mooyer PA Ploegaert I Everts V Evrard P Carmeliet P Dewerchin M Schoonjans L Duran M Impaired neuronal migration and endochondral ossification in Pex7 knockout mice: a model for rhizomelic chondrodysplasia punctata Hum Mol Genet 2003 12 2255 2267 12915479 source