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Article Dans Une Revue Frontiers in Cellular Neuroscience Année : 2021

The Cellular Prion Protein—ROCK Connection: Contribution to Neuronal Homeostasis and Neurodegenerative Diseases

Résumé

Amyloid-based neurodegenerative diseases such as prion, Alzheimer's, and Parkinson's diseases have distinct etiologies and clinical manifestations, but they share common pathological events. These diseases are caused by abnormally folded proteins (pathogenic prions PrP Sc in prion diseases, β-amyloids/Aβ and Tau in Alzheimer's disease, α-synuclein in Parkinson's disease) that display β-sheet-enriched structures, propagate and accumulate in the nervous central system, and trigger neuronal death. In prion diseases, PrP Sc -induced corruption of the physiological functions exerted by normal cellular prion proteins (PrP C ) present at the cell surface of neurons is at the root of neuronal death. For a decade, PrP C emerges as a common cell surface receptor for other amyloids such as Aβ and α-synuclein, which relays, at least in part, their toxicity. In lipid-rafts of the plasma membrane, PrP C exerts a signaling function and controls a set of effectors involved in neuronal homeostasis, among which are the RhoA-associated coiled-coil containing kinases (ROCKs). Here we review (i) how PrP C controls ROCKs, (ii) how PrP C -ROCK coupling contributes to neuronal homeostasis, and (iii) how the deregulation of the PrP C -ROCK connection in amyloid-based neurodegenerative diseases triggers a loss of neuronal polarity, affects neurotransmitter-associated functions, contributes to the endoplasmic reticulum stress cascade, renders diseased neurons highly sensitive to neuroinflammation, and amplifies the production of neurotoxic amyloids.
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Dates et versions

hal-03413479 , version 1 (10-11-2021)

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B Schneider, Anne Baudry, Mathéa Pietri, Aurélie Alleaume-Butaux, Chloé Bizingre, et al.. The Cellular Prion Protein—ROCK Connection: Contribution to Neuronal Homeostasis and Neurodegenerative Diseases. Frontiers in Cellular Neuroscience, 2021, 15, pp.660683. ⟨10.3389/fncel.2021.660683⟩. ⟨hal-03413479⟩
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