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Clinical Autonomic Research
Erschienen in: Clinical Autonomic Research 1/2015

01.02.2015 | Review Article

Novel therapeutic approaches in multiple system atrophy

verfasst von: Jose-Alberto Palma, Horacio Kaufmann

Erschienen in: Clinical Autonomic Research | Ausgabe 1/2015

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Abstract

Multiple system atrophy (MSA) is a sporadic, adult onset, relentlessly progressive neurodegenerative disease characterized by autonomic abnormalities associated with parkinsonism, cerebellar dysfunction, pyramidal signs, or combinations thereof. Treatments that can halt or reverse the progression of MSA have not yet been identified. MSA is neuropathologically defined by the presence of α-synuclein-containing inclusions, particularly in the cytoplasm of oligodendrocytes (glial cytoplasmic inclusions, GCIs), which are associated with neurodegeneration. The mechanisms by which oligodendrocytic α-synuclein inclusions cause neuronal death in MSA are not completely understood. The MSA neurodegenerative process likely comprises cell-to-cell transmission of α-synuclein in a prion-like manner, α-synuclein aggregation, increased oxidative stress, abnormal expression of tubulin proteins, decreased expression of neurotrophic factors, excitotoxicity and microglial activation, and neuroinflammation. In an attempt to block each of these pathogenic mechanisms, several pharmacologic approaches have been tried and shown to exert neuroprotective effects in transgenic mouse or cellular models of MSA. These include sertraline, paroxetine, and lithium, which hamper arrival of α-synuclein to oligodendroglia; rifampicin, lithium, and non-steroidal anti-inflammatory drugs, which inhibit α-synuclein aggregation in oligodendrocytes; riluzole, rasagiline, fluoxetine and mesenchymal stem cells, which exert neuroprotective actions; and minocycline and intravenous immunoglobulins, which reduce neuroinflammation and microglial activation. These and other potential therapeutic strategies for MSA are summarized in this review.
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Metadaten
Titel
Novel therapeutic approaches in multiple system atrophy
verfasst von
Jose-Alberto Palma
Horacio Kaufmann
Publikationsdatum
01.02.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Clinical Autonomic Research / Ausgabe 1/2015
Print ISSN: 0959-9851
Elektronische ISSN: 1619-1560
DOI
https://doi.org/10.1007/s10286-014-0249-7

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