Neuron
Volume 108, Issue 5, 9 December 2020, Pages 822-842
Journal home page for Neuron

Review
ALS Genetics: Gains, Losses, and Implications for Future Therapies

https://doi.org/10.1016/j.neuron.2020.08.022Get rights and content
Under an Elsevier user license
open archive

Summary

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder caused by the loss of motor neurons from the brain and spinal cord. The ALS community has made remarkable strides over three decades by identifying novel familial mutations, generating animal models, elucidating molecular mechanisms, and ultimately developing promising new therapeutic approaches. Some of these approaches reduce the expression of mutant genes and are in human clinical trials, highlighting the need to carefully consider the normal functions of these genes and potential contribution of gene loss-of-function to ALS. Here, we highlight known loss-of-function mechanisms underlying ALS, potential consequences of lowering levels of gene products, and the need to consider both gain and loss of function to develop safe and effective therapeutic strategies.

Keywords

ALS
loss of function
gain of function
C9ORF72
TDP-43
TARDBP
FUS
SOD1
TBK1
OPTN

Cited by (0)

4

These authors contributed equally

5

Lead Contact