The relationship between the 20S proteasomes and prion-mediated neurodegenerations: potential therapeutic opportunities

Abstract

The dysfunction of cellular degradation pathways of aberrant and misfolded proteins is a critical event in the onset of neurodegenerative disorders. Among these pathologies, prion diseases are a unique class of transmissible fatal disorders affecting mammals, characterized by the presence of an abnormal isoform of a membrane-bound protein, namely the prion protein. The proteasome is the main proteolytic machinery in charge of removing damaged, oxidized and misfolded proteins and numerous authors have approached the involvement of this complex in the prion protein cellular processing. Herein, we described the general features of prion disorders focusing our attention on the available data on the interplay between the infectious agent and the proteasome system, exploring its implications in prion-mediated toxicity. Finally, considering the proteasome as a potential drug target, we reviewed possible therapeutic opportunities in the treatment of such pathologies.

Analysis of the Neuroproteome Associated With Cell Therapy After Intranigral Grafting in a Mouse Model of Parkinson Disease

“…Indeed, there is increasing evidence that PrP C , a cellular glycoprotein encoded by PRNP gene, plays important roles in neuroprotection (Linden, 2017). However, aggregates of misfolded PrP C were reported to block axonal transport, intervene in neurotransmission, or induce apoptotic pathways (Cecarini et al, 2010;Halliday et al, 2014). PrPc was further proposed to regulate striatal dopaminergic transmission through alterations of DA receptors (Rial et al, 2014).…”

Editorial: apoptosis in the aging brain

“…Conceivably, such a process substantially challenges the cellular protein handling systems, and primarily the UPS. Eleuteri et al [35] discuss several interesting lines of evidence supporting this notion, indicating that UPS dysfunction may contribute to prion aggregation and resultant cell toxicity, and suggesting potential UPS-targeted therapeutic strategies for this fatal neurological disorder.…”