CoChat
Sign Up
Cited by 199Autophagy in Disease and TherapyAlzheimer's disease research and treatmentsAmyotrophic Lateral Sclerosis Research

Autophagy in neurodegenerative disorders: pathogenic roles and therapeutic implications

Open access
Banerjee, Rebecca, Beal, M. Flint, Thomas, Bobby·2010·Trends in Neurosciences
DOI 10.1016/j.tins.2010.09.001PMC PMC2981680
Open this paper in CoChat — free account

Abstract

Autophagy is a highly conserved intracellular pathway involved in the elimination of proteins and organelles by lysosomes. Known originally as an adaptive response to nutrient deprivation in mitotic cells, autophagy is now recognized as an arbiter of neuronal survival and death decisions in neurodegenerative diseases. Studies using postmortem human tissue, genetic and toxin-induced animal and cellular models indicate that many of the etiological factors associated with neurodegenerative disorders can perturb the autophagy process. Emerging data support the view that dysregulation of autophagy might play a critical role in the pathogenesis of neurodegenerative disorders. In this review, we highlight the pathophysiological roles of autophagy and its potential therapeutic implications in debilitating neurodegenerative disorders, including amyotrophic lateral sclerosis and Alzheimer's, Parkinson's and Huntington's diseases.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.tins.2010.09.001

Cites

16 of 16 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 77

  1. [1]Mizushima N 2007 Autophagy: process and function Genes Dev 21 2861 2873 18006683
  2. [2]Shintani T Klionsky DJ 2004 Autophagy in health and disease: a double-edged sword Science 306 990 995 15528435 PMC1705980
  3. [3]Mizushima N 2008 Autophagy fights disease through cellular self-digestion Nature 451 1069 1075 18305538 PMC2670399
  4. [4]Galluzzi L 2007 Cell death modalities: classification and pathophysiological implications Cell Death Differ 14 1237 1243 17431418
  5. [5]Debnath J 2005 Does autophagy contribute to cell death? Autophagy 1 66 74 16874022
  6. [6]Wong E Cuervo AM 2010 Autophagy gone awry in neurodegenerative diseases Nat Neurosci 13 805 811 20581817 PMC4038747
  7. [7]De Duve C 1963 The lysosome Sci Am 208 64 72 14025755
  8. [8]Klionsky DJ 2007 Autophagy: from phenomenology to molecular understanding in less than a decade Nat Rev Mol Cell Biol 8 931 937 17712358
  9. [9]Axe EL 2008 Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum J Cell Biol 182 685 701 18725538 PMC2518708
  10. [10]Simonsen A Tooze SA 2009 Coordination of membrane events during autophagy by multiple class III PI3-kinase complexes J Cell Biol 186 773 782 19797076 PMC2753151
  11. [11]Hailey DW 2010 Mitochondria supply membranes for autophagosome biogenesis during starvation Cell 141 656 667 20478256 PMC3059894
  12. [14]Todde V 2009 Autophagy: principles and significance in health and disease Biochim Biophys Acta 1792 3 13 19022377
  13. [15]Massey AC 2006 Chaperone-mediated autophagy in aging and disease Curr Top Dev Biol 73 205 235 16782460
  14. [16]Kon M Cuervo AM 2010 Chaperone-mediated autophagy in health and disease FEBS Lett 584 1399 1404 20026330 PMC2843772
  15. [17]Nixon RA 2007 Autophagy, amyloidogenesis and Alzheimer disease J Cell Sci 120 4081 4091 18032783
  16. [18]Yu WH 2005 Macroautophagy--a novel Beta-amyloid peptide-generating pathway activated in Alzheimer’s disease J Cell Biol 171 87 98 16203860 PMC2171227
  17. [19]Nixon RA 2005 Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study J Neuropathol Exp Neurol 64 113 122 15751225
  18. [20]Cataldo AM 2004 Presenilin mutations in familial Alzheimer disease and transgenic mouse models accelerate neuronal lysosomal pathology J Neuropathol Exp Neurol 63 821 830 15330337
  19. [21]Lee JH 2010 Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations Cell 141 1146 1158 20541250 PMC3647462
  20. [22]Pickford F 2008 The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice J Clin Invest 118 2190 2199 18497889 PMC2391284
  21. [23]Selkoe DJ 2001 Clearing the brain’s amyloid cobwebs Neuron 32 177 180 11683988
  22. [24]Jaeger PA 2010 Regulation of amyloid precursor protein processing by the Beclin 1 complex PLoS One 5 e11102 20559548 PMC2886067
  23. [25]Hirai K 2001 Mitochondrial abnormalities in Alzheimer’s disease J Neurosci 21 3017 3023 11312286 PMC6762571
  24. [26]Santos RX 2010 A synergistic dysfunction of mitochondrial fission/fusion dynamics and mitophagy in Alzheimer’s disease J Alzheimers Dis 20 Suppl 2 S401 412 20463393 PMC2923835
  25. [27]Wang X 2008 Dynamin-like protein 1 reduction underlies mitochondrial morphology and distribution abnormalities in fibroblasts from sporadic Alzheimer’s disease patients Am J Pathol 173 470 482 18599615 PMC2475784
  26. [28]Wang X 2008 Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins Proc Natl Acad Sci U S A 105 19318 19323 19050078 PMC2614759
  27. [29]Cho DH 2009 S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury Science 324 102 105 19342591 PMC2823371
  28. [30]Caccamo A 2010 Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments J Biol Chem 285 13107 13120 20178983 PMC2857107
  29. [33]Anisimov VN 2010 Rapamycin extends maximal lifespan in cancer-prone mice Am J Pathol 176 2092 2097 20363920 PMC2861075
  30. [34]Thomas B 2009 Parkinson’s disease: from molecular pathways in disease to therapeutic approaches Antioxid Redox Signal 11 2077 2082 19624258 PMC2819797
  31. [35]Levy OA 2009 Cell death pathways in Parkinson’s disease: proximal triggers, distal effectors, and final steps Apoptosis 14 478 500 19165601 PMC2754154
  32. [36]Alvarez-Erviti L 2010 Chaperone-Mediated Autophagy Markers in Parkinson Disease Brains Arch Neurol Aug 9 [Epub ahead of print] 20697033
  33. [37]Webb JL 2003 Alpha-Synuclein is degraded by both autophagy and the proteasome J Biol Chem 278 25009 25013 12719433
  34. [40]Engelender S 2008 Ubiquitination of alpha-synuclein and autophagy in Parkinson’s disease Autophagy 4 372 374 18216494
  35. [41]Martinez-Vicente M 2008 Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy J Clin Invest 118 777 788 18172548 PMC2157565
  36. [42]Yang Q 2009 Regulation of neuronal survival factor MEF2D by chaperone-mediated autophagy Science 323 124 127 19119233 PMC2666000
  37. [43]Banerjee R 2009 Mitochondrial dysfunction in the limelight of Parkinson’s disease pathogenesis Biochim Biophys Acta 1792 651 663 19059336 PMC2867353
  38. [45]Lee JY 2010 Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy J Cell Biol 189 671 679 20457763 PMC2872903
  39. [46]Chu CT 2010 A pivotal role for PINK1 and autophagy in mitochondrial quality control: implications for Parkinson disease Hum Mol Genet 19 R28 37 20385539 PMC2875056
  40. [47]Dagda RK 2009 Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission J Biol Chem 284 13843 13855 19279012 PMC2679485
  41. [48]Vives-Bauza C 2010 PINK1-dependent recruitment of Parkin to mitochondria in mitophagy Proc Natl Acad Sci U S A 107 378 383 19966284 PMC2806779
  42. [49]Sha D 2010 Phosphorylation of parkin by Parkinson disease-linked kinase PINK1 activates parkin E3 ligase function and NF-kappaB signaling Hum Mol Genet 19 352 363 19880420 PMC2796895
  43. [50]Orr HT Zoghbi HY 2007 Trinucleotide repeat disorders Annu Rev Neurosci 30 575 621 17417937
  44. [51]Lansbury PT Lashuel HA 2006 A century-old debate on protein aggregation and neurodegeneration enters the clinic Nature 443 774 779 17051203
  45. [52]Rubinsztein DC 2007 Potential therapeutic applications of autophagy Nat Rev Drug Discov 6 304 312 17396135
  46. [53]Tellez-Nagel I 1974 Studies on brain biopsies of patients with Huntington’s chorea J Neuropathol Exp Neurol 33 308 332 4150800
  47. [54]Sawa A 2005 Huntingtin is cleaved by caspases in the cytoplasm and translocated to the nucleus via perinuclear sites in Huntington’s disease patient lymphoblasts Neurobiol Dis 20 267 274 15890517
  48. [55]Kegel KB 2000 Huntingtin expression stimulates endosomal-lysosomal activity, endosome tubulation, and autophagy J Neurosci 20 7268 7278 11007884 PMC6772788
  49. [56]Kim M 1999 Mutant huntingtin expression in clonal striatal cells: dissociation of inclusion formation and neuronal survival by caspase inhibition J Neurosci 19 964 973 9920660 PMC6782141
  50. [57]Schmelzle T Hall MN 2000 TOR, a central controller of cell growth Cell 103 253 262 11057898
  51. [59]Atwal RS Truant R 2008 A stress sensitive ER membrane-association domain in Huntingtin protein defines a potential role for Huntingtin in the regulation of autophagy Autophagy 4 91 93 17986868
  52. [60]Zheng S 2010 Deletion of the huntingtin polyglutamine stretch enhances neuronal autophagy and longevity in mice PLoS Genet 6 e1000838 20140187 PMC2816686
  53. [62]Shibata M 2006 Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1 J Biol Chem 281 14474 14485 16522639
  54. [63]Metzger S 2010 Age at onset in Huntington’s disease is modified by the autophagy pathway: implication of the V471A polymorphism in Atg7 Hum Genet Aug 10 [Epub ahead of print] 20697744
  55. [65]Li L 2008 Altered macroautophagy in the spinal cord of SOD1 mutant mice Autophagy 4 290 293 18196963
  56. [67]Morimoto N 2007 Increased autophagy in transgenic mice with a G93A mutant SOD1 gene Brain Res 1167 112 117 17689501
  57. [68]Okamoto K 2010 Pathology of protein synthesis and degradation systems in ALS Neuropathology 30 189 193 20102523
  58. [69]Caccamo A 2009 Rapamycin rescues TDP-43 mislocalization and the associated low molecular mass neurofilament instability J Biol Chem 284 27416 27424 19651785 PMC2785671
  59. [71]Pasquali L 2009 Autophagy, lithium, and amyotrophic lateral sclerosis Muscle Nerve 40 173 194 19609902
  60. [72]Crippa V 2010 The small heat shock protein B8 (HspB8) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS) Hum Mol Genet 19 3440 3456 20570967
  61. [73]Siciliano G 2010 Clinical trials for neuroprotection in ALS CNS Neurol Disord Drug Targets 9 305 313 20406180
  62. [74]Spencer B 2009 Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in alpha-synuclein models of Parkinson’s and Lewy body diseases J Neurosci 29 13578 13588 19864570 PMC2812014
  63. [75]Crews L 2010 Selective molecular alterations in the autophagy pathway in patients with Lewy body disease and in models of alpha-synucleinopathy PLoS One 5 e9313 20174468 PMC2824828
  64. [76]Terni B 2007 Mutant ubiquitin and p62 immunoreactivity in cases of combined multiple system atrophy and Alzheimer’s disease Acta Neuropathol 113 403 416 17237936
  65. [78]Gal J 2009 Sequestosome 1/p62 links familial ALS mutant SOD1 to LC3 via an ubiquitin-independent mechanism J Neurochem 111 1062 1073 19765191 PMC2766427
  66. [79]Munch C 2004 Point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS Neurology 63 724 726 15326253
  67. [80]Ravikumar B 2005 Dynein mutations impair autophagic clearance of aggregate-prone proteins Nat Genet 37 771 776 15980862
  68. [81]Kitada T 1998 Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism Nature 392 605 608 9560156
  69. [84]Kawajiri S 2010 PINK1 is recruited to mitochondria with parkin and associates with LC3 in mitophagy FEBS Lett 584 1073 1079 20153330
  70. [85]Berger Z 2006 Rapamycin alleviates toxicity of different aggregate-prone proteins Hum Mol Genet 15 433 442 16368705
  71. [86]Sarkar S 2007 Small molecules enhance autophagy and reduce toxicity in Huntington’s disease models Nat Chem Biol 3 331 338 17486044 PMC2635561
  72. [87]Ravikumar B 2003 Raised intracellular glucose concentrations reduce aggregation and cell death caused by mutant huntingtin exon 1 by decreasing mTOR phosphorylation and inducing autophagy Hum Mol Genet 12 985 994 12700167
  73. [88]Fornai F 2008 Autophagy and amyotrophic lateral sclerosis: The multiple roles of lithium Autophagy 4 527 530 18367867
  74. [89]Sarkar S 2005 Lithium induces autophagy by inhibiting inositol monophosphatase J Cell Biol 170 1101 1111 16186256 PMC2171537
  75. [90]Sarkar S Rubinsztein DC 2006 Inositol and IP3 levels regulate autophagy: biology and therapeutic speculations Autophagy 2 132 134 16874097
  76. [91]Sarkar S 2007 Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein J Biol Chem 282 5641 5652 17182613
  77. [93]Rodriguez-Navarro JA 2010 Trehalose ameliorates dopaminergic and tau pathology in parkin deleted/tau overexpressing mice through autophagy activation Neurobiol Dis 39 423 438 20546895

Cited by

Sorted by citations

Authors
Banerjee, R., Beal, M. F., & Thomas, B.
Affiliations
Cornell University (US)
Corresponding author
Thomas, Bobby
ORCID
Venue
Trends in Neurosciences
Publisher
Elsevier BV
Published
2010-12
Volume
33
Issue
12
Pages
541-549
ISSN
0166-2236 (ISSN-L)
DOI
10.1016/j.tins.2010.09.001
PMC
PMC2981680
OpenAlex
W2053215139
Cited by
199
References
16
Citations by year
2026: 2 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 9 · 2021: 11 · 2020: 16 · 2019: 14 · 2018: 14 · 2017: 15 · 2016: 12 · 2015: 25 · 2014: 15 · 2013: 23 · 2012: 18
FWCI
1.93
Type
journal article
Language
en
Open access
Licence
Locations
  • Trends in Neurosciences (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Michael J. Fox Foundation for Parkinson's Research
  • National Institutes of Health (ES017295, NS060885, NS062165)
  • U.S. Department of Defense
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
autophagy, neurodegenerative diseases, lysosomal degradation, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, autophagy dysregulation, neurodegeneration pathogenesis, autophagy-targeted therapy
MeSH terms
Autophagy, Humans, Stress, Physiological, Neurodegenerative Diseases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review