Fly for ALS: Drosophila modeling on the route to amyotrophic lateral sclerosis modifiers
- 28 July 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in Cellular and Molecular Life Sciences
- Vol. 78 (17-18), 6143-6160
- https://doi.org/10.1007/s00018-021-03905-8
Abstract
Amyotrophic lateral sclerosis (ALS) is a rare, devastating disease, causing movement impairment, respiratory failure and ultimate death. A plethora of genetic, cellular and molecular mechanisms are involved in ALS signature, although the initiating causes and progressive pathological events are far from being understood. Drosophila research has produced seminal discoveries for more than a century and has been successfully used in the past 25 years to untangle the process of ALS pathogenesis, and recognize potential markers and novel strategies for therapeutic solutions. This review will provide an updated view of several ALS modifiers validated in C9ORF72, SOD1, FUS, TDP-43 and Ataxin-2 Drosophila models. We will discuss basic and preclinical findings, illustrating recent developments and novel breakthroughs, also depicting unsettled challenges and limitations in the Drosophila-ALS field. We intend to stimulate a renewed debate on Drosophila as a screening route to identify more successful disease modifiers and neuroprotective agents.Keywords
Funding Information
- Ministero della Salute
This publication has 208 references indexed in Scilit:
- Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional studyThe Lancet Neurology, 2012
- Nuclear localization sequence of FUS and induction of stress granules by ALS mutantsNeurobiology of Aging, 2011
- Building an ommatidium one cell at a timeDevelopmental Dynamics, 2011
- Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALSNeuron, 2011
- A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTDNeuron, 2011
- Expression of human FUS protein in Drosophila leads to progressive neurodegenerationProtein & Cell, 2011
- Exome Sequencing Reveals VCP Mutations as a Cause of Familial ALSNeuron, 2010
- Sam68 sequestration and partial loss of function are associated with splicing alterations in FXTAS patientsThe EMBO Journal, 2010
- The Microprocessor complex mediates the genesis of microRNAsNature, 2004
- Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosisNature, 1993