المؤلفون: Julia A. Callender, Alexandra C. Newton

المصدر: Neuronal Signaling

مصطلحات موضوعية: 0301 basic medicine, Programmed cell death, Biology, Molecular Bases of Health & Disease, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, medicine, Review Articles, Loss function, Protein kinase C, Diacylglycerol kinase, chemistry.chemical_classification, posttranslational modification, Post-Translational Modifications, Molecular Interactions, Neurodegeneration, neurodegeneration, Cancer, Alzheimer's disease, medicine.disease, Cell biology, 030104 developmental biology, Enzyme, chemistry, Mutation, 030217 neurology & neurosurgery, Neuroscience, protein kinase C

الوصف: Protein kinase C (PKC) is a family of enzymes whose members transduce a large variety of cellular signals instigated by the receptor-mediated hydrolysis of membrane phospholipids. While PKC has been widely implicated in the pathology of diseases affecting all areas of physiology including cancer, diabetes, and heart disease—it was discovered, and initially characterized, in the brain. PKC plays a key role in controlling the balance between cell survival and cell death. Its loss of function is generally associated with cancer, whereas its enhanced activity is associated with neurodegeneration. This review presents an overview of signaling by diacylglycerol (DG)-dependent PKC isozymes in the brain, and focuses on the role of the Ca2+-sensitive conventional PKC isozymes in neurodegeneration.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1961077473400d72c05372787f79392eTest
https://doi.org/10.1042/ns20160005Test

المؤلفون: Elizabeth A. Roberts, Jessica E. Young, Mariah Dunlap, Lawrence S.B. Goldstein, Sol M. Reyna, Rik van der Kant, Grace Woodruff, Julia A. Callender

المصدر: Cell Reports, Vol 17, Iss 3, Pp 759-773 (2016)

مصطلحات موضوعية: 0301 basic medicine, PS1, Mutant, Endocytic cycle, Induced Pluripotent Stem Cells, Endocytic recycling, GTPase, Biology, Endocytosis, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Amyloid beta-Protein Precursor, Alzheimer Disease, medicine, Presenilin-1, endocytosis, Humans, RNA, Messenger, Axon, lcsh:QH301-705.5, Neurons, iPSC, FAD, Phenotype, Axons, Cell biology, Lipoproteins, LDL, 030104 developmental biology, medicine.anatomical_structure, Biochemistry, Transcytosis, lcsh:Biology (General), nervous system, rab GTP-Binding Proteins, Mutation, lipids (amino acids, peptides, and proteins), Amyloid Precursor Protein Secretases, APP, Alzheimer’s disease, Low Density Lipoprotein Receptor-Related Protein-1

الوصف: We investigated early phenotypes caused by familial Alzheimer’s Disease (fAD) mutations in isogenic human iPSC-derived neurons. Analysis of neurons carrying fAD PS1 or APP mutations introduced using genome editing technology at the endogenous loci revealed that fAD mutant neurons had previously unreported defects in the recycling state of endocytosis and soma-to-axon transcytosis of APP and lipoproteins. The endocytosis reduction could be rescued through treatment with a β-secretase inhibitor. Our data suggest that accumulation of β-CTF fragments of APP, but not Aβ, slow vesicle formation from an endocytic recycling compartment marked by the transcytotic GTPase Rab11. We confirm previous results that endocytosis is affected in AD, and extend these to uncover a neuron-specific defect. Decreased lipoprotein endocytosis and transcytosis to the axon suggests that a neuron-specific impairment in endocytic axonal delivery of lipoproteins and other key materials might compromise synaptic maintenance in fAD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::895ced638bc54630b5f43dd30c9d963dTest
https://europepmc.org/articles/PMC5796664Test/

المؤلفون: Basavaraj Hooli, Roberto Malinow, Michael Leitges, Kristina Mullin, Corina E. Antal, Alexandra C. Newton, Mathew A. Sherman, Julia A. Callender, Sylvain Lesné, Stephanie Alfonso, Rudolph E. Tanzi

المصدر: Science signaling, vol 9, iss 427

مصطلحات موضوعية: 0301 basic medicine, Aging, Hippocampus, Neurodegenerative, Alzheimer's Disease, medicine.disease_cause, Biochemistry, Synapse, Mice, Neoplasms, Chlorocebus aethiops, 2.1 Biological and endogenous factors, Aetiology, Mutation, Genome, COS cells, Neurodegenerative Diseases, Cell biology, Neurological, COS Cells, Alzheimer's disease, Human, Protein Kinase C-alpha, PDZ domain, Biology, Article, 03 medical and health sciences, Protein Domains, Alzheimer Disease, Acquired Cognitive Impairment, Genetics, medicine, Animals, Humans, Protein kinase A, Molecular Biology, Protein kinase C, Family Health, Genome, Human, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Cell Biology, medicine.disease, Brain Disorders, 030104 developmental biology, Synapses, Dementia, Biochemistry and Cell Biology

الوصف: Alzheimer’s disease (AD) is a progressive dementia disorder characterized by synaptic degeneration and amyloid-β (Aβ) accumulation in the brain. Through whole-genome sequencing of 1345 individuals from 410 families with late-onset AD (LOAD), we identified three highly penetrant variants in PRKCA , the gene that encodes protein kinase Cα (PKCα), in five of the families. All three variants linked with LOAD displayed increased catalytic activity relative to wild-type PKCα as assessed in live-cell imaging experiments using a genetically encoded PKC activity reporter. Deleting PRKCA in mice or adding PKC antagonists to mouse hippocampal slices infected with a virus expressing the Aβ precursor CT100 revealed that PKCα was required for the reduced synaptic activity caused by Aβ. In PRKCA −/− neurons expressing CT100, introduction of PKCα, but not PKCα lacking a PDZ interaction moiety, rescued synaptic depression, suggesting that a scaffolding interaction bringing PKCα to the synapse is required for its mediation of the effects of Aβ. Thus, enhanced PKCα activity may contribute to AD, possibly by mediating the actions of Aβ on synapses. In contrast, reduced PKCα activity is implicated in cancer. Hence, these findings reinforce the importance of maintaining a careful balance in the activity of this enzyme.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::12358b725c679c77ebbb2178a3b2af05Test
https://europepmc.org/articles/PMC5154619Test/