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Physico-Pathologic Mechanisms Involved in Neurodegeneration: Misfolded Protein-Plasma Membrane Interactions.
Neuron. 2017 Jul 05; 95(1):33-50.N

Abstract

Several neurodegenerative disorders, such as Alzheimer's and Parkinson's disease, are characterized by prominent loss of synapses and neurons associated with the presence of abnormally structured or misfolded protein assemblies. Cell-to-cell transfer of misfolded proteins has been proposed for the intra-cerebral propagation of these diseases. When released, misfolded proteins diffuse in the 3D extracellular space before binding to the plasma membrane of neighboring cells, where they diffuse on a 2D plane. This reduction in diffusion dimension and the cell surface molecular crowding promote deleterious interactions with native membrane proteins, favoring clustering and further aggregation of misfolded protein assemblies. These processes open up new avenues for therapeutics development targeting the initial interactions of deleterious proteins with the plasma membrane or the subsequent pathological signaling.

Authors+Show Affiliations

École Normale Supérieure, Institut de Biologie de l'ENS (IBENS), INSERM, CNRS, PSL Research University, 46 Rue d'Ulm, 75005 Paris, France; Paris-Saclay Institute of Neuroscience, CNRS, Batiments 32-33, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.Department of Women and Children's Health, Science for Life Laboratory, Karolinska Institutet, 1031 Stockholm, Sweden. Electronic address: anita.aperia@ki.se.Paris-Saclay Institute of Neuroscience, CNRS, Batiments 32-33, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France. Electronic address: ronald.melki@cnrs.fr.École Normale Supérieure, Institut de Biologie de l'ENS (IBENS), INSERM, CNRS, PSL Research University, 46 Rue d'Ulm, 75005 Paris, France. Electronic address: triller@biologie.ens.fr.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

28683268

Citation

Shrivastava, Amulya Nidhi, et al. "Physico-Pathologic Mechanisms Involved in Neurodegeneration: Misfolded Protein-Plasma Membrane Interactions." Neuron, vol. 95, no. 1, 2017, pp. 33-50.
Shrivastava AN, Aperia A, Melki R, et al. Physico-Pathologic Mechanisms Involved in Neurodegeneration: Misfolded Protein-Plasma Membrane Interactions. Neuron. 2017;95(1):33-50.
Shrivastava, A. N., Aperia, A., Melki, R., & Triller, A. (2017). Physico-Pathologic Mechanisms Involved in Neurodegeneration: Misfolded Protein-Plasma Membrane Interactions. Neuron, 95(1), 33-50. https://doi.org/10.1016/j.neuron.2017.05.026
Shrivastava AN, et al. Physico-Pathologic Mechanisms Involved in Neurodegeneration: Misfolded Protein-Plasma Membrane Interactions. Neuron. 2017 Jul 5;95(1):33-50. PubMed PMID: 28683268.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Physico-Pathologic Mechanisms Involved in Neurodegeneration: Misfolded Protein-Plasma Membrane Interactions. AU - Shrivastava,Amulya Nidhi, AU - Aperia,Anita, AU - Melki,Ronald, AU - Triller,Antoine, PY - 2016/07/19/received PY - 2017/05/12/revised PY - 2017/05/19/accepted PY - 2017/7/7/entrez PY - 2017/7/7/pubmed PY - 2017/8/2/medline KW - Alzheimer KW - Parkinson KW - membrane interaction KW - pathogenic proteins KW - prion-like propagation KW - protein diffusion KW - protein-aggregation SP - 33 EP - 50 JF - Neuron JO - Neuron VL - 95 IS - 1 N2 - Several neurodegenerative disorders, such as Alzheimer's and Parkinson's disease, are characterized by prominent loss of synapses and neurons associated with the presence of abnormally structured or misfolded protein assemblies. Cell-to-cell transfer of misfolded proteins has been proposed for the intra-cerebral propagation of these diseases. When released, misfolded proteins diffuse in the 3D extracellular space before binding to the plasma membrane of neighboring cells, where they diffuse on a 2D plane. This reduction in diffusion dimension and the cell surface molecular crowding promote deleterious interactions with native membrane proteins, favoring clustering and further aggregation of misfolded protein assemblies. These processes open up new avenues for therapeutics development targeting the initial interactions of deleterious proteins with the plasma membrane or the subsequent pathological signaling. SN - 1097-4199 UR - https://www.unboundmedicine.com/medline/citation/28683268/Physico_Pathologic_Mechanisms_Involved_in_Neurodegeneration:_Misfolded_Protein_Plasma_Membrane_Interactions_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0896-6273(17)30464-6 DB - PRIME DP - Unbound Medicine ER -