Involvement of molecular chaperone in protein-misfolding brain diseases

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 147, С. 112647 - 112647

Опубликована: Фев. 8, 2022

Protein misfolding causes aggregation and build-up in a variety of brain diseases. There are numeral molecules that linked with the protein homeostasis mechanism. Molecular chaperones one such responsible for protection against misfolded aggregation-induced neurotoxicity. Many studies have explored participation molecular Parkinson's disease, Alzheimer's Amyotrophic lateral sclerosis, Huntington's In this review, we highlighted constructive role neurological diseases characterized by their capability to control aberrant interactions at an early stage thus successfully suppressing pathogenic cascades. A comprehensive understanding associated basis involvement chaperone cellular stress might lead progress new therapeutic intrusion-related aggregation.

Язык: Английский

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Alzheimer’s Disease: Models and Molecular Mechanisms Informing Disease and Treatments

Bioengineering, Год журнала: 2024, Номер 11(1), С. 45 - 45

Опубликована: Янв. 1, 2024

Alzheimer’s Disease (AD) is a complex neurodegenerative disease resulting in progressive loss of memory, language and motor abilities caused by cortical hippocampal degeneration. This review captures the landscape understanding AD pathology, diagnostics, current therapies. Two major mechanisms direct pathology: (1) accumulation amyloid β (Aβ) plaque (2) tau-derived neurofibrillary tangles (NFT). The most common variants Aβ pathway APP, PSEN1, PSEN2 are largely responsible for early-onset (EOAD), while MAPT, APOE, TREM2 ABCA7 have modifying effect on late-onset (LOAD). More recent studies implicate chaperone proteins degrading AD. Several tests, such as cognitive function, brain imaging, cerebral spinal fluid (CSF) blood used diagnosis. Additionally, several biomarkers seem to unique specific combination expression could potentially be improved, less invasive diagnostics. In addition genetic perturbations, environmental influences, altered gut microbiome signatures, affect Effective treatments been challenging develop. Currently, there FDA approved drugs (cholinesterase inhibitors, Aß-targeting antibodies an NMDA antagonist) that mitigate rate decline symptoms distress.

Язык: Английский

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Polyglutamine (PolyQ) Diseases: Navigating the Landscape of Neurodegeneration

ACS Chemical Neuroscience, Год журнала: 2024, Номер 15(15), С. 2665 - 2694

Опубликована: Июль 12, 2024

Polyglutamine (polyQ) diseases are a group of inherited neurodegenerative disorders caused by expanded cytosine-adenine-guanine (CAG) repeats encoding proteins with abnormally polyglutamine tract. A total nine polyQ have been identified, including Huntington's disease, six spinocerebellar ataxias, dentatorubral pallidoluysian atrophy (DRPLA), and spinal bulbar muscular (SBMA). The this class each considered rare, yet constitute the largest monogenic disorders. While subtype has its own causative gene, certain pathologic molecular attributes implicated in virtually all diseases, protein aggregation, proteolytic cleavage, neuronal dysfunction, transcription dysregulation, autophagy impairment, mitochondrial dysfunction. Although animal models disease available helping to understand their pathogenesis access disease-modifying therapies, there is neither cure nor prevention for these only symptomatic treatments available. In paper, we analyze data from CAS Content Collection summarize research progress diseases. We examine publication landscape area effort provide insights into current knowledge advances developments. review most discussed concepts assess strategies combat Finally, inspect clinical applications products against development pipelines. objective broad overview evolving regarding outline challenges, evaluate growth opportunities further efforts combating

Язык: Английский

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Amyloid-induced neurodegeneration: A comprehensive review through aggregomics perception of proteins in health and pathology

Ageing Research Reviews, Год журнала: 2024, Номер 96, С. 102276 - 102276

Опубликована: Март 16, 2024

Язык: Английский

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Forcing the Antitumor Effects of HSPs Using a Modulated Electric Field

Cells, Год журнала: 2022, Номер 11(11), С. 1838 - 1838

Опубликована: Июнь 4, 2022

The role of Heat Shock Proteins (HSPs) is a “double-edged sword” with regards to tumors. location and interactions HSPs determine their pro- or antitumor activity. present review includes an overview the relevant functions HSPs, which could improve Promoting processes assist in local systemic management cancer. We explore possibility achieving this by manipulating electromagnetic within tumor microenvironment. An appropriate electric field may select affect cancer cells using heterogeneity tissue. This describes method proposed effect such changes: amplitude-modulated radiofrequency (amRF) applied 13.56 MHz carrier frequency. summarize preclinical investigations amRF on malignant cells. studies show promotion expression HSP70 plasma membrane, participating immunogenic cell death (ICD) pathway. sequence guided molecular changes triggers innate adaptive immune reactions. promotes secretion also extracellular matrix. accompanied free HMGB1 membrane-expressed calreticulin (CRT) form damage-associated patterns encouraging dendritic cells’ maturing for antigen presentation. process CD8+ killer T-cells. Clinical results demonstrate potential trigger effect. conclude that properly HSP activity, situ, it support tumor-specific effects produced locally but acting systemically disseminated metastatic lesions.

Язык: Английский

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Flanking regions, amyloid cores, and polymorphism: the potential interplay underlying structural diversity

Journal of Biological Chemistry, Год журнала: 2023, Номер 299(9), С. 105122 - 105122

Опубликована: Авг. 1, 2023

The β-sheet-rich amyloid core is the defining feature of protein aggregates associated with neurodegenerative disorders. Recent investigations have revealed that there exist multiple examples same protein, sequence, forming a variety cores distinct structural characteristics. These variants, termed as polymorphs, are hypothesized to influence pathological profile and progression different diseases, giving rise unique phenotypic differences. Thus, identifying origin properties these variants remain focus studies, preliminary step in development therapeutic strategies. Here, we review potential role flanking regions inducing polymorphism. regions, adjacent cores, show preponderance for being structurally disordered, imbuing them functional promiscuity. dynamic nature can then manifest form conformational polymorphism aggregates. We take closer look at sequences followed by polymorphic well-characterized proteins amyloid-β, α-synuclein, Tau, TDP-43. also consider factors potentially aggregate structure how be viewed novel targets strategies utilizing their properties.

Язык: Английский

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Neurodevelopmental Disorders (NDD) Caused by Genomic Alterations of the Ubiquitin-Proteasome System (UPS): the Possible Contribution of Immune Dysregulation to Disease Pathogenesis

Frontiers in Molecular Neuroscience, Год журнала: 2021, Номер 14

Опубликована: Сен. 8, 2021

Over thirty years have passed since the first description of ubiquitin-positive structures in brain patients suffering from Alzheimer’s disease. Meanwhile, intracellular accumulation ubiquitin-modified insoluble protein aggregates has become an indisputable hallmark neurodegeneration. However, role ubiquitin and a fortiori ubiquitin-proteasome system (UPS) pathogenesis neurodevelopmental disorders (NDD) is much less described. In this article, we review all reported monogenic forms NDD caused by lesions genes coding for any component UPS including ubiquitin-activating (E1), -conjugating (E2) enzymes, ligases (E3), hydrolases, ubiquitin-like modifiers as well proteasome subunits. Strikingly, our analysis revealed that vast majority these proteins described function negative regulation innate immune response. work, hypothesize possible involvement autoinflammation pathogenesis. Herein, discuss parallels between dysregulation neurodevelopment with aim at improving understanding biology providing knowledge required design novel therapeutic strategies.

Язык: Английский

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Heterogeneous Heat Absorption Is Complementary to Radiotherapy

Cancers, Год журнала: 2022, Номер 14(4), С. 901 - 901

Опубликована: Фев. 11, 2022

(1) Background: Hyperthermia in oncology conventionally seeks the homogeneous heating of tumor mass. The expected isothermal condition is basis dose calculation clinical practice. My objective to study and apply a heterogenic temperature pattern during process show how it supports radiotherapy. (2) Methods: targeted tissue's natural electric thermal heterogeneity used for selective cancer cells. amplitude-modulated radiofrequency current focuses energy absorption on membrane rafts malignant partly "nonthermally" excites heats absorbing protein complexes. (3) Results: excitation transmembrane proteins induces an extrinsic caspase-dependent apoptotic pathway, while heat stress promotes intrinsic independent signals generated by mitochondria. molecular changes synergize method with radiotherapy promote abscopal effect. mild average (39-41 °C) intensifies blood flow promoting oxygenation combination preclinical experiences verify, studies validate method. (4) Conclusions: heterogenic, targeting has similarities DNA strand-breaking controlled allows using similar (J/kg). two therapies are synergistically combined.

Язык: Английский

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Modulating liquid–liquid phase separation of FUS: mechanisms and strategies

Journal of Materials Chemistry B, Год журнала: 2022, Номер 10(42), С. 8616 - 8628

Опубликована: Янв. 1, 2022

This review summarizes the regulations of liquid–liquid phase separation involving fused in sarcoma protein (FUS) by physical stimuli, biochemical modulators and structural modifications.

Язык: Английский

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Tau liquid–liquid phase separation is modulated by the Ca²⁺‐switched chaperone activity of the S100B protein

Journal of Neurochemistry, Год журнала: 2023, Номер 166(1), С. 76 - 86

Опубликована: Янв. 9, 2023

Aggregation of the microtubule-associated protein tau is implicated in several neurodegenerative tauopathies including Alzheimer's disease (AD). Recent studies evidenced liquid-liquid phase separation (LLPS) into droplets as an early event pathogenesis with potential to enhance aggregation. Tauopathies like AD are accompanied by sustained neuroinflammation and release alarmins at stages inflammatory responses encompass protective functions. The Ca

Язык: Английский

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