Fly research and neurodegenerative diseases

Research articles related to ALS and Alzheimer's disease

Baldwin KR, Godena VK, Hewitt VL, Whitworth AJ. Axonal transport defects are a common phenotype in Drosophila models of ALS. Hum Mol Genet. 2016 Jun 15;25(12):2378-2392. Epub 2016 Apr 7. PMID: 27056981; PMCID: PMC5181624.

From the abstract: "Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of motor neurons resulting in a catastrophic loss of motor function. Current therapies are severely limited owing to a poor mechanistic understanding of the pathobiology. Mutations in a large number of genes have now been linked to ALS, including SOD1, TARDBP (TDP-43), FUS and C9orf72. Functional analyses of these genes and their pathogenic mutations have provided great insights into the underlying disease mechanisms. Defective axonal transport is hypothesized to be a key factor in the selective vulnerability of motor nerves ... Here, we assessed the axonal transport of different cargos in multiple Drosophila models of ALS. ... These results further support defects in axonal transport as a common factor in models of ALS that may contribute to the pathogenic process."

Bernstein AI, Lin Y, Street RC, Lin L, Dai Q, Yu L, Bao H, Gearing M, Lah JJ, Nelson PT, He C, Levey AI, Mullé JG, Duan R, Jin P. 5-Hydroxymethylation-associated epigenetic modifiers of Alzheimer's disease modulate Tau-induced neurotoxicity. Hum Mol Genet. 2016 Jun 15;25(12):2437-2450. PMID: 27060332; PMCID: PMC5181627.

From the abstract: "Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive deterioration of cognitive function. Pathogenesis of AD is incompletely understood; evidence suggests a role for epigenetic regulation, in particular the cytosine modifications 5-methylcytosine and 5-hydroxymethylcytosine (5hmC). 5hmC is enriched in the nervous system and displays neurodevelopment and age-related changes. To determine the role of 5hmC in AD, we performed genome-wide analyses of 5hmC in DNA from prefrontal cortex of post-mortem AD patients, and RNA-Seq to correlate changes in 5hmC with transcriptional changes. We identified 325 genes containing differentially hydroxymethylated loci (DhMLs) in both discovery and replication datasets. ... Finally, using an existing AD fly model, we showed some of these genes modulate AD-associated toxicity. ..."

And a review related to Parkinson's disease

Voigt A, Berlemann LA, Winklhofer KF. The mitochondrial kinase PINK1: functions beyond mitophagy. J Neurochem. 2016 Oct;139 Suppl 1:232-239. PMID: 27251035.

From the abstract: "Mutations in the genes encoding the mitochondrial kinase PINK1 and the E3 ubiquitin ligase Parkin cause autosomal recessive Parkinson's disease (PD). Pioneering work in Drosophila melanogaster revealed that the loss of PINK1 or Parkin function causes similar phenotypes including dysfunctional mitochondria. Further research showed that PINK1 can act upstream of Parkin in a mitochondrial quality control pathway to induce removal of damaged mitochondria in a process called mitophagy. ... In this review, we summarize and discuss the functional roles of PINK1 in maintaining mitochondrial integrity, eliminating damaged mitochondria, and promoting cell survival. This article is part of a special issue on Parkinson disease."