title: Could intracrine biology play a role in the pathogenesis of transmissable spongiform encephalopathies, Alzheimer's disease and other neurodegenerative diseases?
abstract: Transmissible spongiform encephalopathies have been shown to result from the misfolding of normal cellular prion proteins in neurons caused by a transmissible abnormal form of the protein. In recent years, similar transmission of abnormal proteins capable of inducing abnormal folding of their normal homologues has been reported in other neurological disorders including Alzheimer's disease, Parkinson's disease and the so-called tauopathies. Thus, a new paradigm--the notion that some neurodegenerative disorders are protein "foldopathies"--has gained wide support. In addition, over recent years, the notion that some intercellular signaling proteins/peptides are intracrines--that is, they can in some instances act within their cells of synthesis or within target cells--has also gained currency. Tenets of this intracrine physiology/action have been developed. Here, it is argued that the protein functionalities demonstrated by foldopathy-related proteins are similar to intracrine actions and that these disorders could be intracrine in nature. If correct, this proposal would have therapeutic implications.
authors.affiliation: Research Division, Ochsner Clinic Foundation, Ochsner Health System, New Orleans, Louisiana.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Re
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000378:metabolism; D017096:Prion Diseases / Q000209:etiology* / Q000378:metabolism; D011328:Prions / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D057165:Proteostasis Deficiencies / Q000209:etiology / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011328:Prions; D003300:Copper