Abnormal protein aggregation and neurodegenerative diseases

2001 ◽  
Vol 46 (1) ◽  
pp. 1-3 ◽  
Author(s):  
Hongyu Hu
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Aggregation ◽  
Abnormal Protein

scholarly journals Lipid Metabolism Influence on Neurodegenerative Disease Progression: Is the Vehicle as Important as the Cargo?

2021 ◽  
Vol 14 ◽  
Author(s):  
Raja Elizabeth Estes ◽  
Bernice Lin ◽  
Arnav Khera ◽  
Marie Ynez Davis
Keyword(s):  
Lipid Metabolism ◽  
Neurodegenerative Diseases ◽  
Protein Aggregation ◽  
Neurodegenerative Disease ◽  
Disease Progression ◽  
Protein Aggregates ◽  
Disease Etiology ◽  
Abnormal Protein ◽  
System A ◽  
Novel Therapeutic

Many neurodegenerative diseases are characterized by abnormal protein aggregates, including the two most common neurodegenerative diseases Alzheimer’s disease (AD) and Parkinson’s disease (PD). In the global search to prevent and treat diseases, most research has been focused on the early stages of the diseases, including how these pathogenic protein aggregates are initially formed. We argue, however, that an equally important aspect of disease etiology is the characteristic spread of protein aggregates throughout the nervous system, a key process in disease progression. Growing evidence suggests that both alterations in lipid metabolism and dysregulation of extracellular vesicles (EVs) accelerate the spread of protein aggregation and progression of neurodegeneration, both in neurons and potentially in surrounding glia. We will review how these two pathways are intertwined and accelerate the progression of AD and PD. Understanding how lipid metabolism, EV biogenesis, and EV uptake regulate the spread of pathogenic protein aggregation could reveal novel therapeutic targets to slow or halt neurodegenerative disease progression.

scholarly journals Observation of liquid-liquid phase separation of ataxin-3 and quantitative evaluation of its concentration in a single droplet using Raman microscopy

2021 ◽  
Author(s):  
Kazuki Murakami ◽  
Shinji Kajimoto ◽  
Daiki Shibata ◽  
Kunisato Kuroi ◽  
Fumihiko Fujii ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Neurodegenerative Diseases ◽  
Protein Aggregation ◽  
Quantitative Evaluation ◽  
Raman Microscopy ◽  
Liquid Phase Separation ◽  
Biological Processes ◽  
Single Droplet ◽  
Liquid Liquid Phase Separation

Liquid–liquid phase separation (LLPS) plays an important role in a variety of biological processes and is also associated with protein aggregation in neurodegenerative diseases. Quantification of LLPS is necessary to...

The Cryo-EM Effect: Structural Biology of Neurodegenerative Disease Proteostasis Factors

2021 ◽  
Author(s):  
Benjamin C Creekmore ◽  
Yi-Wei Chang ◽  
Edward B Lee
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Aggregation ◽  
Neurodegenerative Disease ◽  
Electron Tomography ◽  
Ubiquitin Proteasome System ◽  
26S Proteasome ◽  
X Ray Crystallography ◽  
New Information ◽  
A Cell ◽  
Regulate Protein

Abstract Neurodegenerative diseases are characterized by the accumulation of misfolded proteins. This protein aggregation suggests that abnormal proteostasis contributes to aging-related neurodegeneration. A better fundamental understanding of proteins that regulate proteostasis may provide insight into the pathophysiology of neurodegenerative disease and may perhaps reveal novel therapeutic opportunities. The 26S proteasome is the key effector of the ubiquitin-proteasome system responsible for degrading polyubiquitinated proteins. However, additional factors, such as valosin-containing protein (VCP/p97/Cdc48) and C9orf72, play a role in regulation and trafficking of substrates through the normal proteostasis systems of a cell. Nonhuman AAA+ ATPases, such as the disaggregase Hsp104, also provide insights into the biochemical processes that regulate protein aggregation. X-ray crystallography and cryo-electron microscopy (cryo-EM) structures not bound to substrate have provided meaningful information about the 26S proteasome, VCP, and Hsp104. However, recent cryo-EM structures bound to substrate have provided new information about the function and mechanism of these proteostasis factors. Cryo-EM and cryo-electron tomography data combined with biochemical data have also increased the understanding of C9orf72 and its role in maintaining proteostasis. These structural insights provide a foundation for understanding proteostasis mechanisms with near-atomic resolution upon which insights can be gleaned regarding the pathophysiology of neurodegenerative diseases.

scholarly journals Amyloid diseases: Abnormal protein aggregation in neurodegeneration

1999 ◽  
Vol 96 (18) ◽  
pp. 9989-9990 ◽  
Author(s):  
E. H. Koo ◽  
P. T. Lansbury ◽  
J. W. Kelly
Keyword(s):  
Protein Aggregation ◽  
Abnormal Protein ◽  
Amyloid Diseases

scholarly journals Proteinopathies and OXPHOS dysfunction in neurodegenerative diseases

2017 ◽  
Vol 216 (12) ◽  
pp. 3917-3929 ◽  
Author(s):  
Hibiki Kawamata ◽  
Giovanni Manfredi
Keyword(s):  
Nervous System ◽  
Oxidative Phosphorylation ◽  
Neurodegenerative Diseases ◽  
Gene Mutations ◽  
Misfolded Proteins ◽  
Protein Homeostasis ◽  
Abnormal Protein ◽  
Oxidative Phosphorylation System ◽  
Intermediate Metabolism

Mitochondria participate in essential processes in the nervous system such as energy and intermediate metabolism, calcium homeostasis, and apoptosis. Major neurodegenerative diseases are characterized pathologically by accumulation of misfolded proteins as a result of gene mutations or abnormal protein homeostasis. Misfolded proteins associate with mitochondria, forming oligomeric and fibrillary aggregates. As mitochondrial dysfunction, particularly of the oxidative phosphorylation system (OXPHOS), occurs in neurodegeneration, it is postulated that such defects are caused by the accumulation of misfolded proteins. However, this hypothesis and the pathological role of proteinopathies in mitochondria remain elusive. In this study, we critically review the proposed mechanisms whereby exemplary misfolded proteins associate with mitochondria and their consequences on OXPHOS.

scholarly journals Protein Targets of Oxidative Damage in Human Neurodegenerative Diseases with Abnormal Protein Aggregates

2010 ◽  
Vol 20 (2) ◽  
pp. 281-297 ◽  
Author(s):  
Anna Martínez ◽  
Manuel Portero-Otin ◽  
Reinald Pamplona ◽  
Isidre Ferrer
Keyword(s):  
Oxidative Damage ◽  
Neurodegenerative Diseases ◽  
Protein Aggregates ◽  
Protein Targets ◽  
Abnormal Protein

scholarly journals Supersaturation is a major driving force for protein aggregation in neurodegenerative diseases

2015 ◽  
Vol 36 (2) ◽  
pp. 72-77 ◽  
Author(s):  
Prajwal Ciryam ◽  
Rishika Kundra ◽  
Richard I. Morimoto ◽  
Christopher M. Dobson ◽  
Michele Vendruscolo
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Aggregation ◽  
Driving Force

Biochemical and immunological aspects of protein aggregation in neurodegenerative diseases

2014 ◽  
Vol 11 (6) ◽  
pp. 1503-1512 ◽  
Author(s):  
Fatemeh Shojaei ◽  
Naemeh Tavakolinia ◽  
Adeleh Divsalar ◽  
Thomas Haertlé ◽  
Ali Akbar Saboury ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Aggregation
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