Open AccessPhenotypic diversity in ALS and the role of poly-conformational protein misfolding
Author(s) -
Jacob I. Ayers,
David R. Borchelt
Publication year - 2020
Publication title -
acta neuropathologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.183
H-Index - 170
eISSN - 1432-0533
pISSN - 0001-6322
DOI - 10.1007/s00401-020-02222-x
Subject(s) - amyotrophic lateral sclerosis , phenotype , biology , disease , protein folding , protein aggregation , prion protein , genetics , neurodegeneration , neuroscience , microbiology and biotechnology , gene , medicine , pathology
In many types of familial amyotrophic lateral sclerosis (fALS), mutations cause proteins to gain toxic properties that mediate neurodegenerative processes. It is becoming increasingly clear that the proteins involved in ALS, and those responsible for a host of other neurodegenerative diseases, share many characteristics with a growing number of prion diseases. ALS is a heterogenous disease in which the majority of cases are sporadic in their etiology. Studies investigating the inherited forms of the disease are now beginning to provide evidence that some of this heterogeneity may be due to the existence of distinct conformations that ALS-linked proteins can adopt to produce the equivalent of prion strains. In this review, we discuss the in vitro and in vivo evidence that has been generated to better understand the characteristics of these proteins and how their tertiary structure may impact the disease phenotype.