Abstract
Misfolding of alpha-synuclein (aSyn), formation of toxic oligomers, and their prion like spread are considered key mechanisms of disease pathogenesis in multiple system atrophy. Disease modifying approaches are aimed at interfering with this and related processes, and several of these approaches are currently at different stages of development. These include lowering of aSyn using antisense oligonucleotides or immune system activation with αSyn-mimicking peptides; inhibition of oligomer misfolding using small molecules; blocking of the extracellular spread of aSyn with monoclonal antibodies; enhancing clearance and autophagy with mTOR inhibitors; correction of neurotrophic factor deficiency with mesenchymal stem cells; reduction of neuroinflammation using myeloperoxidase inhibition or inhibition of the inflammasome; addressing the associated dysfunctional iron metabolism using iron chelation; and correcting the associated dysfunctional glucose metabolism and mitochondrial dysfunction. These novel approaches have become possible with improved understanding of disease pathogenesis and will hopefully eventually lead to success in demonstrating clinically meaningful disease modification.
Original language | English (US) |
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Title of host publication | Primer on the Autonomic Nervous System, Fourth Edition |
Publisher | Elsevier |
Pages | 825-830 |
Number of pages | 6 |
ISBN (Electronic) | 9780323854924 |
ISBN (Print) | 9780323854931 |
DOIs | |
State | Published - Jan 1 2022 |
Keywords
- Autophagy
- Clinical trial
- Insulin resistance
- Mitochondria
- Monoclonal antibodies
- Multiple system atrophy
- Myeloperoxidase
- Neuroinflammation
- Neurotrophic factors
- α-Synuclein oligomer
ASJC Scopus subject areas
- General Medicine
- General Neuroscience