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

Abstract

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-β (Aβ), tau, and α-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 Aβ 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 Aβ oligomers (AβOs) and PrPC. Also, we studied the role of PrPC as an AβO receptor that initiates an AβO-induced signal cascade involving mGluR5, Fyn, Pyk2, and eEF2K linking Aβ and tau pathologies, resulting in the death of neurons in the central nervous system. Finally, we have described how the PrPC-AβOs interaction can be used as a new potential therapeutic target for the treatment of PrPC-dependent AD.

Prion Protein: The Molecule of Many Forms and Faces

“…PrP C is a receptor of Fyn kinase, a member of the Src family of tyrosine kinases (SFKs) [146]. Through Fyn kinase activation, PrP C mediates oligomer-induced toxicity in neurodegenerative diseases [147][148][149][150] and promotes neurite outgrowth by the phosphorylation of the GluN2A domain of the neuronal cell adhesion molecule (NCAM) [151]. Fyn kinase and other members of the SFK family are involved in ischemic damage [152][153][154][155].…”

The effect of histidine behaviors on the structural properties of Aβ(1–42) peptide in protonation stage one, two, and three

“…The misfolding, aggregation, and expansion of proteins in the brain that results in neuronal death is a prevalent cause and pathogenic process of neurodegenerative disorders. [1][2][3][4][5] Since the underlying cause of Alzheimer's disease (AD) has not been identified, 1,2,4,6 there is currently no effective treatment for this neurodegenerative disease, which is also sometimes regarded as a kind of dementia. 7 AD affects more than five million Americans, and the prevalence of the condition is rising.…”

Non-Coding RNAs as Novel Regulators of Neuroinflammation in Alzheimer’s Disease

“…Several hypotheses have been proposed to explain the actual pathological development of AD ( 5 ). One of the earliest of these was the cholinergic hypothesis.…”