Abstract
Many neurodegenerative diseases are late onset diseases, associated with aggregation of proteins, implying that aged cells are more susceptible to proteotoxic stress. It is known that with aging, there is a decline in the functionality of chaperone networks and on the other hand, accumulation of damaged proteins occurs. Together, this has a cumulative effects on cellular protein homeostasis. Several studies have revealed that availability of DNAJ proteins, the cochaperones to the Hsp70 machine, could be a rate-limiting factor in handling diseased proteins within the cell. In this review, we highlight how DNAJ proteins can affect aggregation of disease-causing proteins, if and how this depends on their function as Hsp70 co-chaperones, and how much this depends on the type of protein causing the disease. Finally, we will discuss the five known degenerative diseases that are linked to mutations in individual DNAJ members and what mechanism may underlie these DNAJ chaperonopathies.
Keywords: Protein aggregation diseases, DNAJ proteins, neurodegeneration, Hsp70, chaperonopathies, protein quality control
Current Topics in Medicinal Chemistry
Title:DNAJ Proteins and Protein Aggregation Diseases
Volume: 12 Issue: 22
Author(s): Vaishali Kakkar, Louis C. B. Prins and Harm H. Kampinga
Affiliation:
Keywords: Protein aggregation diseases, DNAJ proteins, neurodegeneration, Hsp70, chaperonopathies, protein quality control
Abstract: Many neurodegenerative diseases are late onset diseases, associated with aggregation of proteins, implying that aged cells are more susceptible to proteotoxic stress. It is known that with aging, there is a decline in the functionality of chaperone networks and on the other hand, accumulation of damaged proteins occurs. Together, this has a cumulative effects on cellular protein homeostasis. Several studies have revealed that availability of DNAJ proteins, the cochaperones to the Hsp70 machine, could be a rate-limiting factor in handling diseased proteins within the cell. In this review, we highlight how DNAJ proteins can affect aggregation of disease-causing proteins, if and how this depends on their function as Hsp70 co-chaperones, and how much this depends on the type of protein causing the disease. Finally, we will discuss the five known degenerative diseases that are linked to mutations in individual DNAJ members and what mechanism may underlie these DNAJ chaperonopathies.
Export Options
About this article
Cite this article as:
Kakkar Vaishali, C. B. Prins Louis and H. Kampinga Harm, DNAJ Proteins and Protein Aggregation Diseases, Current Topics in Medicinal Chemistry 2012; 12 (22) . https://dx.doi.org/10.2174/1568026611212220004
DOI https://dx.doi.org/10.2174/1568026611212220004 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
- 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
- Announcements
Related Articles
-
Targeted Drug Delivery in Brain Tumors-nanochemistry Applications and Advances
Current Topics in Medicinal Chemistry Natural compound-derived epigenetic regulators targeting epigenetic readers, writers and erasers
Current Topics in Medicinal Chemistry Pulmonary Neuroendocrine Cell System in Health and Disease
Current Respiratory Medicine Reviews Pleiotropic Effects of Statins: Stabilization of the Vulnerable Atherosclerotic Plaque?
Current Pharmaceutical Design Protein Structure Based Strategies for Antigen Discovery and Vaccine Development Against Malaria and Other Pathogens
Endocrine, Metabolic & Immune Disorders - Drug Targets Future of Cardiac Pacemaker – an Update of Biological Pacemaker Patents
Recent Patents on Biomedical Engineering (Discontinued) Pharmacologic Therapy In Traumatic Brain Injury: Update On Experimental Treatment Strategies
Current Pharmaceutical Design Omentin: Linking Metabolic Syndrome and Cardiovascular Disease
Current Vascular Pharmacology Inhibitors and Breakers of Advanced Glycation Endproducts (AGEs): A Review
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents The Value of Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Anxiety Disorders: An Integrative Review
CNS & Neurological Disorders - Drug Targets Editorial (Thematic Issue: Frontiers in Atherosclerosis, Heart Disease and Diabetes)
Cardiovascular & Hematological Disorders-Drug Targets A Review on Hematopoietic Stem Cell Treatment for Epilepsy
CNS & Neurological Disorders - Drug Targets Anesthetic Considerations for Electroconvulsive Therapy-Especially Hemodynamic and Respiratory Management
Current Psychiatry Reviews Fetal Protein Restriction, Taurine and Islet Plasticity
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Development of RNA Aptamer-Based Therapeutic Agents
Current Medicinal Chemistry Ovarian Hyperstimulation Syndrome: The Best Approaches for Preven-tion and Treatment: A Mini-Review
Current Women`s Health Reviews Cannabinoid System in Neurodegeneration: New Perspectives in Alzheimers Disease
Mini-Reviews in Medicinal Chemistry A New Perspective of Cannabinoid 1 Receptor Antagonists: Approaches Toward Peripheral CB1R Blockers without Crossing the Blood-Brain Barrier
Current Topics in Medicinal Chemistry Current Advances in L-DOPA and DOPA-Peptidomimetics: Chemistry, Applications and Biological Activity
Current Medicinal Chemistry Dendritic Cell Immunotherapy for Acute Inflammatory Diseases
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry