miR-10b-5p expression in Huntington’s disease brain relates to age of onset and the extent of striatal involvement

In the paper

“support the presence and robust up-regulation of Hox-related miRNAs in HD brain [13].”

What the sources say

• Supported

  The Results section (“Five miRNAs are up-regulated in HD”) reports significant up-regulation in HD prefrontal cortex, including a 28.41-fold increase for miR-10b-5p. The Discussion section (“miR-10b-5p, miR-196a-5p, miR-196b-5p and miR-615-3p implicate Hox cluster genes”) identifies four of the five up-regulated miRNAs as Hox-cluster-related. The claim is supported for the HD brain tissue studied. (LLM, conf=0.94)

  cites [13] Hoss AG, Kartha VK, Dong X, Latourelle JC, Dumitriu A, Hadzi TC, et al. MicroRNAs located in the Hox gene clusters are implicated in huntington’s disease pathogenesis. PLoS Genet. 2014;10(2):e1004188. source

In the paper

“While onset age is unequivocally related to the size of the expanded CAG repeat, with longer repeats leading to earlier onset, only 50% to 70% of the variation can be attributed to repeat size [3,4].”

What the sources say

• Partly supported

  The Abstract says expanded CAG repeat size partly explains variation in HD age at onset, and the paper adjusts onset age for repeat size in its analysis. The passages do not specify that longer repeats lead to earlier onset, so that direction of the relationship is not verified by our copy. (LLM, conf=0.78)

  cites [3] Li JL, Hayden MR, Almqvist EW, Brinkman RR, Durr A, Dode C, et al. A genome scan for modifiers of age at onset in Huntington disease: the HD MAPS study. Am J Hum Genet. 2003;73(3):682–7. sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [4] Djousse L, Knowlton B, Hayden M, Almqvist EW, Brinkman R, Ross C, et al. Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease. Am J Med Genet A. 2003;119A(3):279–82. source

In the paper

“Huntington’s disease (HD) is an inherited disorder caused by a CAG trinucleotide repeat expansion in HTT which leads to progressive motor and cognitive impairment due to the gradual loss of neurons within striatal and cortical brain regions [1].”

What the sources say

• Partly supported

  The Introduction describes HD as an inherited, progressive disorder with motor disturbance, cognitive loss, and selective neuronal loss most severe in the caudate and putamen. The Discussion identifies the expanded trinucleotide repeat in the gene it calls IT15 as the likely cause. The cited passages do not identify cortical neuronal loss, so the claim's inclusion of cortical brain regions is not supported by this copy. (LLM, conf=0.86)

  cites [1] HDCRG. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell. 1993;72(6):971–83. sourceExperimental — accuracy not yet measured

In the paper

“In HD, the dysregulation of miRNAs has been reported in HD in vitro models, transgenic HD animals and human HD brain [12-24].”

What the sources say

• ?Not checked — no full text of the sourcecites [12] Gaughwin PM, Ciesla M, Lahiri N, Tabrizi SJ, Brundin P, Bjorkqvist M. Hsa-miR-34b is a plasma-stable microRNA that is elevated in pre-manifest Huntington’s disease. Hum Mol Genet. 2011;20(11):2225–37. source
• Supported

  The Introduction reports altered miRNA expression in cellular and mouse models of HD. The Results section reports five significantly up-regulated miRNAs in human HD prefrontal cortex compared with controls. Page numbers were not provided in the copy. (LLM, conf=0.93)

  cites [13] Hoss AG, Kartha VK, Dong X, Latourelle JC, Dumitriu A, Hadzi TC, et al. MicroRNAs located in the Hox gene clusters are implicated in huntington’s disease pathogenesis. PLoS Genet. 2014;10(2):e1004188. source
• Partly supported

  The Results report altered miRNA expression in transgenic HD mice, and the Discussion describes earlier miRNA findings in postmortem human HD brain. The paper also uses an HD cell model, but the passages found do not report dysregulated miRNA expression in that in vitro model; its miR-200a assay involves transfection. Page numbers were not available in our copy. (LLM, conf=0.84)

  cites [14] Jin J, Cheng Y, Zhang Y, Wood W, Peng Q, Hutchison E, et al. Interrogation of brain miRNA and mRNA expression profiles reveals a molecular regulatory network that is perturbed by mutant huntingtin. J Neurochem. 2012;123(4):477–90. sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [15] Johnson R, Zuccato C, Belyaev ND, Guest DJ, Cattaneo E, Buckley NJ. A microRNA-based gene dysregulation pathway in Huntington’s disease. Neurobiol Dis. 2008;29(3):438–45. source
• Partly supported

  The Introduction cites prior work on brain-enriched miRNAs in disease states, and the References list a study reporting that miR-9/miR-9* is downregulated in Huntington’s disease. Our copy does not specify dysregulation across HD in vitro models, transgenic animals, and human HD brain, so it supports only the broader HD-miRNA point. (LLM, conf=0.78)

  cites [16] Jovicic A, Roshan R, Moisoi N, Pradervand S, Moser R, Pillai B, et al. Comprehensive expression analyses of neural cell-type-specific miRNAs identify new determinants of the specification and maintenance of neuronal phenotypes. J Neurosci. 2013;33(12):5127–37. sourceExperimental — accuracy not yet measured
• Supported

  The Background explicitly reports miRNA dysregulation in HD patients, transgenic HD mice, and in vitro experimental models. The paper also reports dysregulated miRNAs in transgenic HD monkey brains and human HD brain tissue. (LLM, conf=0.94)

  cites [17] Kocerha J, Xu Y, Prucha MS, Zhao D, Chan AW. microRNA-128a dysregulation in transgenic Huntington’s disease monkeys. Molecular Brain. 2014;7:46. source
• ?Not checked — no full text of the sourcecites [18] Lee ST, Chu K, Im WS, Yoon HJ, Im JY, Park JE, et al. Altered microRNA regulation in Huntington’s disease models. Exp Neurol. 2011;227(1):172–9. source
• Supported

  The Methods (Human brain samples) identify the samples as frontal cortex and striatum from HD patients and controls. The Results (miRNA transcriptome deregulation in HD samples) report significantly upregulated and downregulated miRNAs in those samples. This paper supports the human-brain part of the sentence’s grouped citations; the sentence does not specifically assign the in vitro or animal-model findings to this paper. (LLM, conf=0.91)

  cites [19] Marti E, Pantano L, Banez-Coronel M, Llorens F, Minones-Moyano E, Porta S, et al. A myriad of miRNA variants in control and Huntington’s disease brain regions detected by massively parallel sequencing. Nucleic Acids Res. 2010;38(20):7219–35. source
• Partly supported

  The Results section, “miRNA expression changes with HD progression” (page unavailable), reports altered miRNA levels in human HD cortex, supporting the human-brain part of the sentence. The passages from this paper do not establish miRNA dysregulation in HD in vitro models or transgenic HD animals. (LLM, conf=0.86)

  cites [20] Packer AN, Xing Y, Harper SQ, Jones L, Davidson BL. The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington’s disease. J Neurosci. 2008;28(53):14341–6. sourceExperimental — accuracy not yet measured
• Supported

  The Introduction reports altered miRNA expression in a cell model of HD. The Abstract reports decreased miRNA expression in R6/2 HD mice and altered expression in postmortem brains of HD patients, covering all three settings in the claim. (LLM, conf=0.92)

  cites [21] Sinha M, Ghose J, Bhattarcharyya NP. Micro RNA −214,-150,-146a and-125b target Huntingtin gene. RNA Biol. 2011;8(6):1005–21. source

In the paper

“a growth factor required for the survival and differentiation of striatal neurons [40].”

What the sources say

• Partly supported

  The Discussion (page unavailable) says BDNF is important for striatal-neuron survival in vitro, and the paper reports impaired striatal development and maturation after BDNF depletion. It does not establish the unqualified claim that BDNF is required for striatal-neuron survival; its developmental findings support the differentiation part more broadly. (LLM, conf=0.86)

  cites [40] Li Y, Yui D, Luikart BW, McKay RM, Li Y, Rubenstein JL, et al. Conditional ablation of brain-derived neurotrophic factor-TrkB signaling impairs striatal neuron development. Proc Natl Acad Sci U S A. 2012;109(38):15491–6. sourceExperimental — accuracy not yet measured

In the paper

“Differentially expressed miRNAs increased in HD compared to controls tended to have negative correlations with onset and death, and positive correlations with striatal and cortical score.”

In the paper

“In HD, 46 miRNAs were identified as significantly up-regulated and 29 as down-regulated in their expression.”

In the paper

“In a next-generation sequence analysis of small non-coding RNAs in 26 HD and 36 control brains we detected 938 miRNAs and 75 of these were differentially expressed.”

In the paper

“the expression of miRNAs in grade 3 and 4 brains appeared relatively similar to one another, with the exception of miR-10b-5p, as mentioned above, and miR-4488, where grade 3 brains were significantly lower than all other groups”

In the paper

“No significant relationship of the expression of the 75 differentially expressed miRNA to CAG-adjusted cortical score was observed, although nominal associations were seen.”

In the paper

“5712 unique mRNA targets for miRNAs with positive fold change in HD (miR-106a/302a-5p, miR-196a/miR-196b, miR-302a-3p, miR-363, miR-10b, miR-615-3p), and 6572 mRNA targets for negative fold change in HD (miR-129-3p, miR-129-5p, miR-132-3p, miR-4449, miR-4488, miR-490-5p) were found using Targetscan [33]”

What the sources say

• ?Not checked — no full text of the sourcecites [33] Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120(1):15–20. source

In the paper

“Eight of the remaining nine miRNAs that failed to achieve significance had the same direction of effect”

In the paper

“miR-10b-5p was confirmed as significant after correcting for multiple corrections (p-value = 3.0e-10, q-value = 6.6e-9).”

In the paper

“65 miRNA were found to be significant in the ANOVA (FDR-adjusted q-value < 0.05), indicating differential expression may be driven by the difference of controls to specific grades.”

In the paper

“After CAG-adjusted cortical score correction, CAG-adjusted striatal score remained significant (miR-10b-5p p-value = 0.04, miR-10b-3p p-value = 0.01, miR-302a-3p p-value = 0.005).”

In the paper

“Samples from symptomatic individuals had striatal scores ranging 1.43–3.82 and cortical scores ranging from 0.40–2.36”

In the paper

“Grade 0 brains were neuropathologically normal and asymptomatic at the time of death”

In the paper

“the expression of miR-10b-5p was significant in nearly all comparisons; pairwise contrasts between all grades as well as with the control group were different except for grade 0, although grade 0 was different than grades 2, 3 and 4”

In the paper

“the expression of miRNAs in grade 0 brains was rarely different than controls, with the exception of miR-200c-3p, where its expression in grade 0 brains was significantly lower than both controls and grades 2–4 brains”

In the paper

“Fourteen differentially expressed miRNAs were significantly differentially expressed in the replication set and thirteen of these fourteen were significant in the combined sequence analysis.”

In the paper

“In HD and controls, most 5′-3′ miRNA pairs were positively correlated in their expression, with the exception of miR-1298 in HD and miR-10b and miR-302a in controls”

In the paper

“were significantly up-regulated in their expression [21,38].”

In the paper

“Many of these miRNA changes appear present ordinal trends with an increase (miR-10b-5p, miR-10b-3p, miR-302a, miR-196a-5p, miR-196b-5p) or decrease (miR-663b, miR-4488, miR-4449) in their expression across grade.”

In the paper

“Generally, these miRNAs had strong, positive associations to striatal and cortical H-V scores, weak positive association with disease duration and strong negative associations to onset and death age.”

In the paper

“Three miRNAs (miR-10b-3p/5p, miR-302a) related to H-V striatal score, independent of the CAG repeat expansion size and for miR-10b-5p, independent of cortical involvement.”

In the paper

“Down-regulated miRNAs clustered together as well but were less defined in their relationships to clinical features.”

In the paper

“The increased sample size enables the detection of significantly altered miRNAs with lower levels of differential expression as well as more comprehensive characterization of the relationship of these miRNAs to relevant clinical features of the disease”

In the paper

“In the central nervous system (CNS), miRNAs are abundant, as brain-specific miRNAs assist in various neuronal processes such as synaptic development, maturation and plasticity [8,9].”

What the sources say

• ?Not checked — no full text of the sourcecites [8] Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M, et al. A brain-specific microRNA regulates dendritic spine development. Nature. 2006;439(7074):283–9. source
• ?Not checked — no full text of the sourcecites [9] Cao X, Yeo G, Muotri AR, Kuwabara T, Gage FH. Noncoding RNAs in the mammalian central nervous system. Annu Rev Neurosci. 2006;29:77–103. source

In the paper

“The remaining variation is highly heritable (h2 = 0.56), suggesting a strong role for genes that modify disease progression [3].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [3] Li JL, Hayden MR, Almqvist EW, Brinkman RR, Durr A, Dode C, et al. A genome scan for modifiers of age at onset in Huntington disease: the HD MAPS study. Am J Hum Genet. 2003;73(3):682–7. source

In the paper

“varying from age 4 years to age 80 [2].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [2] Myers RH. Huntington’s disease genetics. NeuroRx. 2004;1(2):255–62. source

In the paper

“miRNAs influence a diverse range of cellular processes [7]”

What the sources say

• ?Not checked — no full text of the sourcecites [7] Alvarez-Garcia I, Miska EA. MicroRNA functions in animal development and human disease. Development. 2005;132(21):4653–62. source

In the paper

“H-V scores are a continuous metric and therefore more amenable to adjustment of covariates such as CAG repeat size in modeling of neuropathological involvement and independently assesses striatal and cortical involvement.”

What the sources say

• Not checked yetcites [28] Hadzi TC, Hendricks AE, Latourelle JC, Lunetta KL, Cupples LA, Gillis T, et al. Assessment of cortical and striatal involvement in 523 Huntington disease brains. Neurology. 2012;79(16):1708–15. source

In the paper

“Altered miRNA expression has been observed in diseases of the CNS, particularly in age-dependent neurodegenerative diseases, which suggests that the expression of miRNAs may contribute to neuropathogenesis [10,11].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [10] Gascon E, Gao FB. Cause or effect: misregulation of microRNA pathways in neurodegeneration. Front Neurosci. 2012;6:48. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [11] Junn E, Mouradian MM. MicroRNAs in neurodegenerative diseases and their therapeutic potential. Pharmacol Ther. 2012;133(2):142–50. source

In the paper

“MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate the expression of genes in a sequence-specific manner, binding to the 3′-untranslated region (3′UTR) to initiate cleavage or translational repression of target transcripts [5,6].”

What the sources say

• Not checked yetcites [5] Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97. source
• Not checked yetcites [6] Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(19167326):215–33. source

In the paper

“To avoid confounding the analysis of these clinical features by the known, strong relationship between HTT CAG repeat size and disease pathology and onset [4,28,31,32], CAG-adjusted residuals were calculated for all continuous clinical traits”

What the sources say

• ?Not checked — no full text of the sourcecites [4] Djousse L, Knowlton B, Hayden M, Almqvist EW, Brinkman R, Ross C, et al. Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease. Am J Med Genet A. 2003;119A(3):279–82. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [28] Hadzi TC, Hendricks AE, Latourelle JC, Lunetta KL, Cupples LA, Gillis T, et al. Assessment of cortical and striatal involvement in 523 Huntington disease brains. Neurology. 2012;79(16):1708–15. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [31] Langbehn DR, Hayden MR, Paulsen JS. CAG-repeat length and the age of onset in Huntington disease (HD): a review and validation study of statistical approaches. Am J Med Genet B Neuropsychiatr Genet. 2010;153B(2):397–408. source
• ?Not checked — no full text of the sourcecites [32] Myers RH, Vonsattel JP, Stevens TJ, Cupples LA, Richardson EP, Martin JB, et al. Clinical and neuropathologic assessment of severity in Huntington’s disease. Neurology. 1988;38(3):341–7. source

In the paper

“miR-132 is highly enriched in the brain [34,35]”

What the sources say

• Not checked yetcites [34] Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse. Current Biol CB. 2002;12(9):735–9. source
• Not checked yetcites [35] Miska EA, Alvarez-Saavedra E, Townsend M, Yoshii A, Sestan N, Rakic P, et al. Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biol. 2004;5(9):R68. source

In the paper

“Firefly Bioworks microRNA assay, a multiplexed, particle-based technology using flow cytometry to measure miRNA levels, was used to quantify and orthogonally validate miRNA differential expression from sequencing”

In the paper

“We believe these miRNA signals are not attributed to a change in BA9 architecture, influenced by neuronal cell death or reactive glial response, because cell numbers between HD and controls from the same brain samples were indistinguishable [13,30].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [13] Hoss AG, Kartha VK, Dong X, Latourelle JC, Dumitriu A, Hadzi TC, et al. MicroRNAs located in the Hox gene clusters are implicated in huntington’s disease pathogenesis. PLoS Genet. 2014;10(2):e1004188. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [30] Bai G, Cheung I, Shulha HP, Coelho JE, Li P, Dong X, et al. Epigenetic dysregulation of hairy and enhancer of split 4 (HES4) is associated with striatal degeneration in postmortem Huntington brains. Hum Mol Genet. 2015;24(5):1441–56. source

In the paper

“Concordant with our findings, miR-132-3p down-regulation in human HD parietal cortical tissue [15] and in brains of R6/2 and YAC128 HD mouse models has been observed [15,18].”

What the sources say

• ?Not checked — no full text of the sourcecites [15] Johnson R, Zuccato C, Belyaev ND, Guest DJ, Cattaneo E, Buckley NJ. A microRNA-based gene dysregulation pathway in Huntington’s disease. Neurobiol Dis. 2008;29(3):438–45. source
• ?Not checked — no full text of the sourcecites [18] Lee ST, Chu K, Im WS, Yoon HJ, Im JY, Park JE, et al. Altered microRNA regulation in Huntington’s disease models. Exp Neurol. 2011;227(1):172–9. source

In the paper

“which may consequently lead to death of striatal neurons [42].”

What the sources say

• ?Not checked — no full text of the sourcecites [42] Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, et al. Loss of huntingtin-mediated BDNF gene transcription in Huntington’s disease. Science. 2001;293(5529):493–8. source

In the paper

“over-expression of miR-10b-5p might be harmful to neuronal cells.”

In the paper

“its over-expression in vitro and in animal transgenic models suppressed mutant HTT expression [24].”

What the sources say

• ?Not checked — no full text of the sourcecites [24] Cheng PH, Li CL, Chang YF, Tsai SJ, Lai YY, Chan AW, et al. miR-196a ameliorates phenotypes of Huntington disease in cell, transgenic mouse, and induced pluripotent stem cell models. Am J Hum Genet. 2013;93(2):306–12. source

In the paper

“Another target of miR-132 is acetylcholinesterase (ACHE), which encodes an enzyme responsible for the breakdown of the neurotransmitter acetylcholine at the neural synapse [37].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [37] McGleenon BM, Dynan KB, Passmore AP. Acetylcholinesterase inhibitors in Alzheimer’s disease. Br J Clin Pharmacol. 1999;48(4):471–80. source

In the paper

“miRNAs that target the HTT 3′UTR and reduce HTT transcript levels in vitro, miR-148a-5p, miR-150-5p and miR-214-5p”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [21] Sinha M, Ghose J, Bhattarcharyya NP. Micro RNA −214,-150,-146a and-125b target Huntingtin gene. RNA Biol. 2011;8(6):1005–21. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [38] Kozlowska E, Krzyzosiak WJ, Koscianska E. Regulation of huntingtin gene expression by miRNA-137, −214, −148a, and their respective isomiRs. Int J Mol Sci. 2013;14(8):16999–7016. source

In the paper

“Our findings identify many miRNA alterations in HD brain and a large number of these are related to clinical manifestations of the disease, where the signal is independent of the size of the CAG repeat expansion.”

In the paper

“acetylcholinesterase inhibitors are FDA-approved for the treatment of cognitive impairments in Alzheimer’s disease [37].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [37] McGleenon BM, Dynan KB, Passmore AP. Acetylcholinesterase inhibitors in Alzheimer’s disease. Br J Clin Pharmacol. 1999;48(4):471–80. source

In the paper

“HD samples and controls were not different in postmortem interval (PMI) (p-value = 0.69), RNA integrity number (p-value = 0.08) or gender (p-value = 0.51) but differed in ages at death (HD mean age =59.5, control mean age =68.6; p-value = 0.01) (see Table 1).”

In the paper

“These patterns suggest that decreasing up-regulated miRNAs and increasing down-regulated miRNA may be beneficial.”

In the paper

“Asymptomatic HD samples did not differ in age at death (mean age =67.5) in comparison to HD or control samples (control p-value = 0.92; HD p-value = 0.40).”

In the paper

“Differentially expressed miRNAs may also target HTT transcripts as a response to mutant HTT to reduce HTT transcriptional levels and limit toxicity.”

In the paper

“Acetylcholinesterase is critically involved in cognition”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [37] McGleenon BM, Dynan KB, Passmore AP. Acetylcholinesterase inhibitors in Alzheimer’s disease. Br J Clin Pharmacol. 1999;48(4):471–80. source

In the paper

“Covariates (PMI, RIN, age at death) were not included in linear models, as neither PMI nor RIN were determined to have an effect on the outcome of the results.”

In the paper

“miR-10b-5p has been observed to facilitate neurodifferentiation [43].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [43] Meseguer S, Mudduluru G, Escamilla JM, Allgayer H, Barettino D. MicroRNAs-10a and -10b contribute to retinoic acid-induced differentiation of neuroblastoma cells and target the alternative splicing regulatory factor SFRS1 (SF2/ASF). J Biol Chem. 2011;286(21118818):4150–64. source

In the paper

“Thus, decreased miR-132 levels may negatively impact brain health, through the dysregulation of p250GAP (limiting its suppression) and ACHE (indirectly decreasing acetylcholine levels).”

In the paper

“For the cluster analysis in Figure 4, Pearson correlations for miRNA expression to clinical feature were performed and those miRNAs with p-values < 0.05, without adjustment for multiple comparisons, were reported.”

In the paper

“Age at death could not be included in the analysis due to the relationship of age at death and HD clinical pathology.”

In the paper

“normal huntingtin protein is reported to up-regulate BDNF levels”

What the sources say

• ?Not checked — no full text of the sourcecites [42] Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, et al. Loss of huntingtin-mediated BDNF gene transcription in Huntington’s disease. Science. 2001;293(5529):493–8. source

In the paper

“Disruption to any of these systems may affect neuron health.”

In the paper

“its expression has been shown to affect neuron morphogenesis and enhance neurite outgrowth by suppressing the GTPase-activating protein p250GAP (p250GAP/RICS) [36].”

What the sources say

• Not checked yetcites [36] Vo N, Klein ME, Varlamova O, Keller DM, Yamamoto T, Goodman RH, et al. A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. Proc Natl Acad Sci U S A. 2005;102(45):16426–31. source

In the paper

“we believe this is an issue of statistical power.”

In the paper

“mutant huntingtin impairs BDNF protein abundance”

What the sources say

• ?Not checked — no full text of the sourcecites [42] Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, et al. Loss of huntingtin-mediated BDNF gene transcription in Huntington’s disease. Science. 2001;293(5529):493–8. source

In the paper

“This study was reviewed by the Boston University School of Medicine Institutional Review Board (Protocol H-28974), and was approved as exempt because the study involves only tissue collected post-mortem, and consequently not classified as human subjects.”

In the paper

“Although miR-196a does not directly target HTT [33]”

What the sources say

• ?Not checked — no full text of the sourcecites [33] Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120(1):15–20. source

In the paper

“increased miR-196a expression was observed in a primate model of HD”

What the sources say

• ?Not checked — no full text of the sourcecites [24] Cheng PH, Li CL, Chang YF, Tsai SJ, Lai YY, Chan AW, et al. miR-196a ameliorates phenotypes of Huntington disease in cell, transgenic mouse, and induced pluripotent stem cell models. Am J Hum Genet. 2013;93(2):306–12. source

In the paper

“Up- and down-regulated miRNAs may target genes in similar biological systems, and these genes are involved in transcriptional regulation, neuronal development and other important aspects surrounding neuron function.”