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Cell. Neurosci."],"abstract":"<jats:p>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<jats:sup>Sc<\/jats:sup> in prion diseases, \u03b2-amyloids\/A\u03b2 and Tau in Alzheimer's disease, \u03b1-synuclein in Parkinson's disease) that display \u03b2-sheet-enriched structures, propagate and accumulate in the nervous central system, and trigger neuronal death. In prion diseases, PrP<jats:sup>Sc<\/jats:sup>-induced corruption of the physiological functions exerted by normal cellular prion proteins (PrP<jats:sup>C<\/jats:sup>) present at the cell surface of neurons is at the root of neuronal death. For a decade, PrP<jats:sup>C<\/jats:sup> emerges as a common cell surface receptor for other amyloids such as A\u03b2 and \u03b1-synuclein, which relays, at least in part, their toxicity. In lipid-rafts of the plasma membrane, PrP<jats:sup>C<\/jats:sup> 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<jats:sup>C<\/jats:sup> controls ROCKs, (ii) how PrP<jats:sup>C<\/jats:sup>-ROCK coupling contributes to neuronal homeostasis, and (iii) how the deregulation of the PrP<jats:sup>C<\/jats:sup>-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.<\/jats:p>","DOI":"10.3389\/fncel.2021.660683","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T05:17:50Z","timestamp":1618204670000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["The Cellular Prion Protein\u2014ROCK Connection: Contribution to Neuronal Homeostasis and Neurodegenerative Diseases"],"prefix":"10.3389","volume":"15","author":[{"given":"Benoit","family":"Schneider","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Baudry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Math\u00e9a","family":"Pietri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Alleaume-Butaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chlo\u00e9","family":"Bizingre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Nioche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Kellermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marie","family":"Launay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2147\/CHC.S28081","article-title":"Cellular prion protein is required for neuritogenesis: fine-tuning of multiple signaling pathways involved in focal adhesions and actin cytoskeleton dynamics","volume":"5","author":"Alleaume-Butaux","year":"2013","journal-title":"Cell Health Cytoskeleton"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e1005073","DOI":"10.1371\/journal.ppat.1005073","article-title":"Double-edge sword of sustained ROCK Activation in prion diseases through neuritogenesis defects and prion accumulation","volume":"11","author":"Alleaume-Butaux","year":"2015","journal-title":"PLoS Pathog."},{"key":"B3","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1038\/31729","article-title":"Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase","volume":"393","author":"Arber","year":"1998","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","first-page":"10050","DOI":"10.1038\/s41598-017-10236-x","article-title":"\u03b1-synuclein amyloids hijack prion protein to gain cell entry, facilitate cell-to-cell spreading and block prion replication","volume":"7","author":"Auli\u0107","year":"2017","journal-title":"Sci. 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