A historical review of multiple system atrophy with a critical appraisal of cellular and animal models

David J. Marmion, Wouter Peelaerts, Jeffrey H. Kordower

Research output: Contribution to journalReview articlepeer-review

Abstract

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA), and dysautonomia with cerebellar ataxia or parkinsonian motor features. Isolated autonomic dysfunction with predominant genitourinary dysfunction and orthostatic hypotension and REM sleep behavior disorder are common characteristics of a prodromal phase, which may occur years prior to motor-symptom onset. MSA is a unique synucleinopathy, in which alpha-synuclein (aSyn) accumulates and forms insoluble inclusions in the cytoplasm of oligodendrocytes, termed glial cytoplasmic inclusions (GCIs). The origin of, and precise mechanism by which aSyn accumulates in MSA are unknown, and, therefore, disease-modifying therapies to halt or slow the progression of MSA are currently unavailable. For these reasons, much focus in the field is concerned with deciphering the complex neuropathological mechanisms by which MSA begins and progresses through the course of the disease. This review focuses on the history, etiopathogenesis, neuropathology, as well as cell and animal models of MSA.

Original languageEnglish (US)
Pages (from-to)1507-1527
Number of pages21
JournalJournal of Neural Transmission
Volume128
Issue number10
DOIs
StatePublished - Oct 2021
Externally publishedYes

Keywords

  • Alpha-synuclein
  • Animal models
  • Glioneuronal degeneration
  • Multiple system atrophy
  • Oligodendrocytes
  • Pathology

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

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