Furthermore, while abnormal aggregation of \u03b1syn is the dominant pathological hallmark of synucleinopathies, the nature of \u03b1syn aggregation is distinct between different disorders. For example, PD, Parkinson\u2019s disease dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by \u03b1syn deposits in neuronal Lewy bodies and Lewy neurites, whereas multiple system atrophy (MSA) is defined by abnormal filamentous deposition of \u03b1syn in the nuclei and cytoplasm of both oligodendrocytes and neurons [70-72]. If prion-like \u03b1syn seeding plays an important role in the pathogenesis of neurodegenerative disease then how and why \u03b1syn behaves differently in different diseases must be addressed (see below).<\/p>\n
A final challenge to the prion-like propagation of \u03b1syn pathology accounting for PD is the observation that Lewy pathology is not necessary for nigral degeneration and the clinical presence of parkinsonism. While pathological studies on genetic forms of PD are limited, it is clear that at least some of these patients do not show classic Lewy pathology<\/p>\n
\u00a0<\/span>https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC3776210\/<\/a><\/p>\n \u00a0<\/span>Thus, it is vital that further in vitro<\/i> and in vivo<\/i> studies are performed to validate the potential involvement of \u03b1syn as a prion-like factor and tease out the mechanisms by which \u03b1syn may be responsible for disease progression in the human condition. However, in view of the unresolved challenges highlighted in this review, caution should be taken in uncritically accepting a role for a prion-like process, particularly in all cases of PD. Indeed, the mechanisms contributing to the progression of the disease may be as variable as the disease itself?<\/p>\n https:\/\/pubmed.ncbi.nlm.nih.gov\/29480459\/<\/a><\/p>\n