当前位置： SCI文献检索 > HUMAN MOLECULAR GENETICS期刊下所有文献 > ALS mouse model SOD1G93A displays early pathology of sensory small fibers associated to accumulation of a neurotoxic splice variant of peripherin.

ALS mouse model SOD1G93A displays early pathology of sensory small fibers associated to accumulation of a neurotoxic splice variant of peripherin.

Abstract：

:Growing evidence suggests that amyotrophic lateral sclerosis (ALS) is a multisystem neurodegenerative disease that primarily affects motor neurons and, though less evidently, other neuronal systems. About 75% of sporadic and familial ALS patients show a subclinical degeneration of small-diameter fibers, as measured by loss of intraepidermal nerve fibers (IENFs), but the underlying biological causes are unknown. Small-diameter fibers are derived from small-diameter sensory neurons, located in dorsal root ganglia (DRG), whose biochemical hallmark is the expression of type III intermediate filament peripherin. We tested here the hypothesis that small-diameter DRG neurons of ALS mouse model SOD1(G93A)suffer from axonal stress and investigated the underlying molecular mechanism. We found that SOD1(G93A)mice display small fiber pathology, as measured by IENF loss, which precedes the onset of the disease. In vitro small-diameter DRG neurons of SOD1(G93A)mice show axonal stress features and accumulation of a peripherin splice variant, named peripherin56, which causes axonal stress through disassembling light and medium neurofilament subunits (NFL and NFM, respectively). Our findings first demonstrate that small-diameter DRG neurons of the ALS mouse model SOD1(G93A)display axonal stress in vitro and in vivo, thus sustaining the hypothesis that the effects of ALS disease spread beyond motor neurons. These results suggest a molecular mechanism for the small fiber pathology found in ALS patients. Finally, our data agree with previous findings, suggesting a key role of peripherin in the ALS pathogenesis, thus highlighting that DRG neurons mirror some dysfunctions found in motor neurons.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Sassone J,Taiana M,Lombardi R,Porretta-Serapiglia C,Freschi M,Bonanno S,Marcuzzo S,Caravello F,Bendotti C,Lauria G

doi

10.1093/hmg/ddw035

subject

Has Abstract

pub_date

2016-04-15 00:00:00

pages

1588-99

issue

eissn

0964-6906

issn

1460-2083

pii

ddw035

journal_volume

pub_type

杂志文章

在线工具

ALS mouse model SOD1G93A displays early pathology of sensory small fibers associated to accumulation of a neurotoxic splice variant of peripherin.