Cerebellar long-term depression and auto-immune target of auto-antibodies: the concept of LTDpathies.
Anti-GluR delta antibody
Anti-VGCC antibody
Anti-mGluR antibody
Cerebellar ataxias
Immune-mediated cerebellar ataxias
Long-term depression
Journal
Molecular biomedicine
ISSN: 2662-8651
Titre abrégé: Mol Biomed
Pays: Singapore
ID NLM: 9918283581406676
Informations de publication
Date de publication:
10 Jan 2021
10 Jan 2021
Historique:
received:
07
10
2020
accepted:
07
12
2020
entrez:
10
1
2022
pubmed:
11
1
2022
medline:
11
1
2022
Statut:
epublish
Résumé
There is general agreement that auto-antibodies against ion channels and synaptic machinery proteins can induce limbic encephalitis. In immune-mediated cerebellar ataxias (IMCAs), various synaptic proteins, such as GAD65, voltage-gated Ca channel (VGCC), metabotropic glutamate receptor type 1 (mGluR1), and glutamate receptor delta (GluR delta) are auto-immune targets. Among them, the pathophysiological mechanisms underlying anti-VGCC, anti-mGluR1, and anti-GluR delta antibodies remain unclear. Despite divergent auto-immune and clinical profiles, these subtypes show common clinical features of good prognosis with no or mild cerebellar atrophy in non-paraneoplastic syndrome. The favorable prognosis reflects functional cerebellar disorders without neuronal death. Interestingly, these autoantigens are all involved in molecular cascades for induction of long-term depression (LTD) of synaptic transmissions between parallel fibers (PFs) and Purkinje cells (PCs), a crucial mechanism of synaptic plasticity in the cerebellum. We suggest that anti-VGCC, anti-mGluR1, and anti-GluR delta Abs-associated cerebellar ataxias share one common pathophysiological mechanism: a deregulation in PF-PC LTD, which results in impairment of restoration or maintenance of the internal model and triggers cerebellar ataxias. The novel concept of LTDpathies could lead to improvements in clinical management and treatment of cerebellar patients who show these antibodies.
Identifiants
pubmed: 35006439
doi: 10.1186/s43556-020-00024-x
pii: 10.1186/s43556-020-00024-x
pmc: PMC8607360
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
2Informations de copyright
© 2021. The Author(s).
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