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Translational Neurodegeneration

, 6:15

First Online: 16 June 2017Received: 11 April 2017Accepted: 06 June 2017DOI: 10.1186-s40035-017-0087-3

Cite this article as: Yu, B. & Pamphlett, R. Transl Neurodegener 2017 6: 15. doi:10.1186-s40035-017-0087-3

Abstract

BackgroundAmyotrophic lateral sclerosis ALS is a fatal neurodegenerative disease characterised by a rapid loss of lower and upper motor neurons. As a complex disease, the ageing process and complicated gene-environment interactions are involved in the majority of cases.

Main bodySignificant advances have been made in unravelling the genetic susceptibility to ALS with massively parallel sequencing technologies, while environmental insults remain a suspected but largely unexplored source of risk. Several studies applying the strategy of Mendelian randomisation have strengthened the link between environmental insults and ALS, but none so far has proved conclusive. We propose a new ALS model which links the current knowledge of genetic factors, ageing and environmental insults. This model provides a mechanism as to how ALS is initiated, with environmental insults playing a critical role.

ConclusionThe available evidence has suggested that inherited defects could cause mitochondrial dysfunction, which would establish the primary susceptibility to ALS. Further study of the underlying mechanism may shed light on ALS pathogenesis. Environmental insults are a critical trigger for ALS, particularly in the aged individuals with other toxicant susceptible genes. The identification of ALS triggers could lead to preventive strategies for those individuals at risk.

KeywordsAmyotrophic lateral sclerosis Environmental risk factors Mendelian randomisation Mitochondrial dysfunction Trigger Initiation Spread AbbreviationsALSAmyotrophic lateral sclerosis

HERV-KHuman endogenous retrovirus Group K

SNVSingle nucleotide variants





Author: Bing Yu - Roger Pamphlett

Source: https://link.springer.com/







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