Abstract
Alzheimer’s disease (AD) is characterized by severe cognitive impairment and memory loss. AD is classified both into the “protein conformational” and the “endoplasmic reticulum-mitochondria stress” disorders. AD is a very complex, multifactorial disease of heterogeneous genetic and environmental background. The amyloid hypothesis of AD cannot fully explain the various clinical forms of the disease. Protein folding and misfolding in the endoplasmic reticulum (ER), and accumulation of several misfolded proteins (β-amyloid, Tau, alpha-synuclein, etc.) in ER and mitochondria (MT) may play a key role in the development of AD. Functional degradation of the synapse and the synapse holding neurites represents the first step in the pathogenesis of neurodegeneration. MT and ER are tightly coupled both physically and functionally with a special lipid raft called mitochondria-associated ER-membrane (MAM). MAM is crucial for Ca2+ signalling and metabolic regulation of the cell. In turn, the impairment of ER-MT interplay is a common mechanism of different neurodegenerative diseases. In this review, we discuss recent findings focusing on the protein conformational and metabolic dysfunction, and the role of MAM and ER-MT crosstalk in neurodegeneration.
Keywords: Protein folding, misfolding, refolding chaperones, IDB, unfolded protein response, drug design.
Current Protein & Peptide Science
Title:Protein Folding and Misfolding, Endoplasmic Reticulum Stress in Neurodegenerative Diseases: in Trace of Novel Drug Targets
Volume: 17 Issue: 2
Author(s): Botond Penke, Ferenc Bogár and Lívia Fülöp
Affiliation:
Keywords: Protein folding, misfolding, refolding chaperones, IDB, unfolded protein response, drug design.
Abstract: Alzheimer’s disease (AD) is characterized by severe cognitive impairment and memory loss. AD is classified both into the “protein conformational” and the “endoplasmic reticulum-mitochondria stress” disorders. AD is a very complex, multifactorial disease of heterogeneous genetic and environmental background. The amyloid hypothesis of AD cannot fully explain the various clinical forms of the disease. Protein folding and misfolding in the endoplasmic reticulum (ER), and accumulation of several misfolded proteins (β-amyloid, Tau, alpha-synuclein, etc.) in ER and mitochondria (MT) may play a key role in the development of AD. Functional degradation of the synapse and the synapse holding neurites represents the first step in the pathogenesis of neurodegeneration. MT and ER are tightly coupled both physically and functionally with a special lipid raft called mitochondria-associated ER-membrane (MAM). MAM is crucial for Ca2+ signalling and metabolic regulation of the cell. In turn, the impairment of ER-MT interplay is a common mechanism of different neurodegenerative diseases. In this review, we discuss recent findings focusing on the protein conformational and metabolic dysfunction, and the role of MAM and ER-MT crosstalk in neurodegeneration.
Export Options
About this article
Cite this article as:
Penke Botond, Bogár Ferenc and Fülöp Lívia, Protein Folding and Misfolding, Endoplasmic Reticulum Stress in Neurodegenerative Diseases: in Trace of Novel Drug Targets, Current Protein & Peptide Science 2016; 17 (2) . https://dx.doi.org/10.2174/1389203716666151102104653
DOI https://dx.doi.org/10.2174/1389203716666151102104653 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
TRPC Channels and their Implications for Neurological Diseases
CNS & Neurological Disorders - Drug Targets Alzheimer's Disease and NQO1: Is there a Link?
Current Alzheimer Research GSK-3 Inhibitors as New Leads to Treat Type-II Diabetes
Current Drug Targets Regulation of Cell Death and Survival by Resveratrol: Implications for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Novel Metals and Metal Complexes as Platforms for Cancer Therapy
Current Pharmaceutical Design TP73, An Under-Appreciated Player in Non-Hodgkin Lymphoma Pathogenesis and Management
Current Molecular Medicine NGR-based Strategies for Targeting Delivery of Chemotherapeutics to Tumor Vasculature
Anti-Cancer Agents in Medicinal Chemistry 5-HT3 Receptors
Current Pharmaceutical Design The Therapeutical Potential of a Novel Pterocarpanquinone LQB-118 to Target Inhibitor of Apoptosis Proteins in Acute Myeloid Leukemia Cells
Anti-Cancer Agents in Medicinal Chemistry p35 Deficiency Accelerates HMGB-1-mediated Neuronal Death in the Early Stages of an Alzheimer's disease Mouse Model
Current Alzheimer Research In silico Analysis of Sulpiride, Synthesis, Characterization and In vitro Studies of its Nanoparticle for the Treatment of Schizophrenia
Current Computer-Aided Drug Design LHON: Mitochondrial Mutations and More
Current Genomics The Role of Vasopressin in Affective Disorders: Possible Targets of Intervention
Central Nervous System Agents in Medicinal Chemistry Molecular Targeting of Cell Death Signal Transduction Pathways in Cancer
Current Signal Transduction Therapy Epilepsy, Regulation of Brain Energy Metabolism and Neurotransmission
Current Medicinal Chemistry <sup>11</sup>C-mHED for PET / CT: Principles of Synthesis, Methodology and First Clinical Applications
Current Radiopharmaceuticals Specialisation of the Tropomyosin Composition of Actin Filaments Provides New Potential Targets for Chemotherapy
Current Cancer Drug Targets The Current Chemical Utility of Marine and Terrestrial Filamentous Fungi in Side-Chain Chemistry
Current Organic Chemistry Molecular Basis for the Neuroprotective Properties of FKBP-Binding Immunophilin Ligands
Current Medicinal Chemistry - Central Nervous System Agents Prostaglandin J2 Family and the Cardiovascular System
Current Vascular Pharmacology