Pros and cons of a prion-like pathogenesis in Parkinson's disease

It has recently been found that α-synuclein may behave similarly to the prion precursor and propagate between cells. The post-mortem proof of α-synuclein containing Lewy bodies in embryonic dopamine cells transplants in PD patient suggests that the misfolded protein might be transmitted from the diseased host to donor neurons reminiscent of prion behavior. The involvement of the basal ganglia and brainstem in the degenerative process are other congruencies between Parkinson's and Creutzfeldt-Jakob disease. However, a number of issues advise caution before categorizing Parkinson's disease as a prion disorder, because clinical appearance, brain imaging, cerebrospinal fluid and neuropathological findings exhibit fundamental differences between both disease entities. Most of all, infectiousness, a crucial hallmark of prion diseases, has never been observed in PD so far. Moreover, the cellular propagation of the prion protein has not been clearly defined and it is, therefore, difficult to assess the molecular similarities between the two disease entities.At the current state of knowledge, the molecular pathways of transmissible pathogenic proteins are not yet fully understood. Their exact involvement in the pathophysiology of prion disorders and neurodegenerative diseases has to be further investigated in order to elucidate a possible overlap between both disease categories that are currently regarded as distinct entities.Parkinson's disease (PD) is a sporadic or familial neurodegenerative disorder histopathologically characterized by intraneuronal protein aggregates staining positive for α-synuclein (Lewy Bodies, LB). Concomitant Alzheimer disease type neuropathological features with amyloid deposits and plaques are also frequently found [1]. A recent clinico-pathological study on 242 brain donors with pathologically verified PD showed the presence of neurofibrillary tangles in 47% of cases with non-tremor dominant PD, neocortical amyloid plaque formation in 62% and amy