title: Functional Prions in the Brain.
abstract: Prions are proteins that can adopt self-perpetuating conformations and are traditionally regarded as etiological agents of infectious neurodegenerative diseases in humans, such as Creutzfeldt-Jakob disease, kuru, and transmissible encephalopathies. More recently, a growing consensus has emerged that prion-like, self-templating mechanisms also underlie a variety of neurodegenerative disorders, including amyotrophic lateral sclerosis, Alzheimer's disease, and Huntington's disease. Perhaps most surprising, not all prion-like aggregates are associated with pathological changes. There are now several examples of prion-like proteins in mammals that serve positive biological functions in their aggregated state. In this review, we discuss functional prions in the nervous system, with particular emphasis on the cytoplasmic polyadenylation element-binding protein (CPEB) and the role of its prion-like aggregates in synaptic plasticity and memory. We also mention a more recent example of a functional prion-like protein in the brain, TIA-1, and its role during stress. These studies of functional prion-like proteins have provided a number of generalizable insights on how prion-based protein switches may operate to serve physiological functions in higher eukaryotes.
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Rayman
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, New York 10032.|Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, New York 10032.|Howard Hughes Medical Institute, Chevy Chase, Maryland 20815-6789.|Zuckerman Mind Brain Behavior Institute, New York, New York 10027.|Kavli Institute for Brain Science, New York, New York 10032.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Kandel
mesh_terms: D000818:Animals; D001048:Aplysia; D001921:Brain / Q000378:metabolism*; D004330:Drosophila; D006801:Humans; D008568:Memory; D023421:Models, Animal; D011328:Prions / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D039221:mRNA Cleavage and Polyadenylation Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: C490386:CPEB1 protein, human; D011328:Prions; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors; D012701:Serotonin