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Home arrow Environment arrow Inflammatory Disorders of the Nervous System: Pathogenesis, Immunology, and Clinical Management
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Amyotrophic Lateral Sclerosis (ALS)

A virus link to ALS has long been suspected, as reviewed [96]. However, promising new work suggests that ALS is a protein-misfolding disease. Evidence for involvement of MP/exosomes in the transport of these toxic proteins is given by Bellingham et al. [116]. Mutant superoxide dismutase-1 (SOD-1) was proposed as a candidate culprit in ALS [117], and very recent experiments offer further support in that direction [118]. It is believed that the complement (C) system normally acts to eliminate such aberrant proteins [112]. It is believed that aggregated misfolded protein is the cause of neurodegeneration but Lee et al. question this assumption in ALS [119].

MP, a-Synuclein, and Parkinson's Disease (PD)

The neuron-specific protein, a-synuclein, is recognized as a major player in PD [120, 121]. Plasma exosomes containing a-synuclein likely originate in the CNS and increase in PD [122]. Plasma exosomes were found to accelerate aggregation of a-synuclein [123]. Exosomes isolated from CSF of patients with PD or AD were tested for several miRNA and other markers, including a-synuclein, with significant differences between AD, PD, and normal controls, suggesting use as a diagnostic aid, and involvement in pathogenesis [124]. Most encouraging was the administration of exosomal siRNA against a-synuclein on a murine model, resulting in reduction of a-synuclein aggregates, the presumed cause of neurodegeneration [125]. Related work purports to elucidate the secretion of toxic exosomal [125]. These papers are only a small sampler of literature found on this topic for their review. For example, search of PubMed using “amyloid precursor protein and extracellular vesicles” yields 80 papers on this alone. Thus, MP/exosomes are recognized as major players in these diseases.

 
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