Prions and Neurodegenerative Diseases: A Focus on Alzheimer's Disease

Specific protein misfolding and aggregation are mechanisms underlying various neurodegenerative diseases such as prion disease and Alzheimer's disease (AD). The misfolded proteins are involved in prions, amyloid-beta (A beta), tau, and alpha-synuclein disorders; they share common structural, biological, and biochemical characteristics, as well as similar mechanisms of aggregation and self-propagation. Pathological features of AD include the appearance of plaques consisting of deposition of protein A beta and neurofibrillary tangles formed by the hyperphosphorylated tau protein. Although it is not clear how protein aggregation leads to AD, we are learning that the cellular prion protein (PrPC) plays an important role in the pathogenesis of AD. Herein, we first examined the pathogenesis of prion and AD with a focus on the contribution of PrPC to the development of AD. We analyzed the mechanisms that lead to the formation of a high affinity bond between A beta oligomers (A beta Os) and PrPC. Also, we studied the role of PrPC as an A beta O receptor that initiates an A beta O-induced signal cascade involving mGluR5, Fyn, Pyk2, and eEF2K linking A beta and tau pathologies, resulting in the death of neurons in the central nervous system. Finally, we have described how the PrPC-A beta Os interaction can be used as a new potential therapeutic target for the treatment of PrPC-dependent AD.

Automated summary

Specific protein misfolding and aggregation are mechanisms underlying neurodegenerative diseases such as prion disease and Alzheimer's disease (AD). The misfolded proteins contribute to the pathological features of AD, including the formation of plaques and neurofibrillary tangles. The cellular prion protein (PrPC) has an important role in the pathogenesis of AD.