Beyond the synucleinopathies: alpha synuclein as a driving force in neurodegenerative comorbidities

AbstractThe fundamental role that alpha-synuclein (aSyn) plays in the pathogenesis of neurodegenerative synucleinopathies, including Parkinson ’s disease, dementia with Lewy bodies, and multiple system atrophy, is a well-accepted fact. A wealth of experimental evidence has linked this relatively small but ubiquitously expressed protein to a plethora of cytopathologic mechanisms and suggests that aSyn may be capable of seeding the progres sive spread of synucleinopathy throughout the brain. Beyond the synucleinopathies, the abnormal deposition of aSyn is frequently seen in a variety of other neurodegenerative proteinopathies including Alzheimer’s disease. In spite of the fact that the frequency of concomitant aSyn pathology in thes e disorders is such that it can be considered the rule rather than the exception, the potential role that aSyn may have in these disorders has received relatively little attention.In this article we postulate that aSyn may in fact be a key protein in driving the pathogenic processes in neurodegenerative comorbidities. In addition to reviewing the frequency of concomitant deposition of aSyn in the neurodegenerative proteinopathies, we also consider our current understanding of the interaction of aSyn with other neurodegenerative disease-associated proteins, including tau, TDP-43, amyloid- β and prion protein, in the context of neuropathologic studies describing the anatomical sites of potential concomitant pathology. We conclude that a growing b...

Source: Translational Neurodegeneration - September 3, 2019 Category: Neurology Source Type: research