Revisiting the grammar of Tau aggregation and pathology formation: how new insights from brain pathology are shaping how we study and target Tauopathies

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 51(2), P. 513 - 565

Published: Dec. 10, 2021

We discuss novel approaches for embracing and reproducing complexity of Tau pathology required developing disease-relevant diagnostics effective therapies.

Language: Английский

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Type 2 Diabetes Mellitus and Alzheimer’s Disease: Shared Molecular Mechanisms and Potential Common Therapeutic Targets

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(23), P. 15287 - 15287

Published: Dec. 4, 2022

The global prevalence of diabetes mellitus and Alzheimer's disease is increasing alarmingly with the aging population. Numerous epidemiological data suggest that there a strong association between type 2 an increased risk dementia. These diseases are both degenerative progressive share common factors. amyloid cascade plays key role in pathophysiology disease. accumulation beta peptides gradually leads to hyperphosphorylation tau proteins, which then form neurofibrillary tangles, resulting neurodegeneration cerebral atrophy. In disease, apart from these processes, alteration glucose metabolism insulin signaling brain seems induce early neuronal loss impairment synaptic plasticity, years before clinical manifestation large amount evidence on existence resistance during has led description this as "type 3 diabetes". Available animal models have been valuable understanding relationships but date, mechanistical links poorly understood. non-exhaustive review, we describe main molecular mechanisms may link two diseases, emphasis impaired IGF-1 signaling. We also focus GSK3β DYRK1A, markers closely associated pancreatic β-cell dysfunction diabetes, thus represent therapeutic targets for diseases.

Language: Английский

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Alzheimer's disease: Updated multi-targets therapeutics are in clinical and in progress

European Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 238, P. 114464 - 114464

Published: May 20, 2022

Language: Английский

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Glycogen Synthase Kinase-3 Inhibitors: Preclinical and Clinical Focus on CNS-A Decade Onward

Frontiers in Molecular Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: Jan. 21, 2022

The protein kinase, GSK-3, participates in diverse biological processes and is now recognized a promising drug discovery target treating multiple pathological conditions. Over the last decade, range of newly developed GSK-3 inhibitors chemotypes inhibition modes has been developed. Even more conspicuous dramatic increase indications that were tested from mood behavior disorders, autism cognitive disabilities, to neurodegeneration, brain injury pain. Indeed, clinical pre-clinical studies largely expanded uncovering new mechanisms novel insights into contribution neurodegeneration central nerve system (CNS)-related disorders. In this review we summarize developments field describe use variety CNS This remarkable volume information being generated undoubtedly reflects great interest, as well intense hope, developing potent safe practice.

Language: Английский

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Signal pathways in the treatment of Alzheimer’s disease with traditional Chinese medicine

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 152, P. 113208 - 113208

Published: May 31, 2022

This study aimed to reveal the classical signal pathways and important potential targets of traditional Chinese medicine (TCM) for treating Alzheimer's disease (AD), provide support further investigation on TCM its active ingredients.Literature survey was conducted using PubMed, Web Science, Google Scholar, CNKI, other databases, with "Alzheimer's disease," "traditional medicine," "medicinal herb," "Chinese "natural plant" as primary keywords.TCM could modulate related AD pathological progression, including NF-κB, Nrf2, JAK/STAT, ubiquitin-proteasome pathway, autophagy-lysosome pathway-related AMPK/mTOR, GSK-3/mTOR, PI3K/Akt/mTOR, well SIRT1 PPARα pathway. It regulate crosstalk between through a multitarget, thus maintaining chronic inflammatory interaction balance, inhibiting oxidative stress damage, regulating system function, modulating autophagy, eventually improving cognitive impairment in patients AD.TCM be multilevel, multitargeted, multifaceted prevent treat AD. In-depth research prevention treatment new ideas exploring pathogenesis developing anti-AD drugs.

Language: Английский

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Protective Effects of Bifidobacterium Breve MCC1274 as a Novel Therapy for Alzheimer’s Disease

Nutrients, Journal Year: 2025, Volume and Issue: 17(3), P. 558 - 558

Published: Jan. 31, 2025

Alzheimer’s disease (AD) is the most common form of dementia and characterized by memory impairment that significantly interferes with daily life. Therapeutic options for AD substantively modify progression remain a critical unmet need. In this regard, gut microbiota crucial in maintaining human health regulating metabolism immune responses, increasing evidence suggests probiotics, particularly beneficial bacteria, can enhance cognitive functions. Recent studies have highlighted positive effects Bifidobacterium breve MCC1274 (B. MCC1274) on individuals mild (MCI) schizophrenia. Additionally, oral supplementation B. has been shown to effectively prevent decline AppNL–G–F mice. relation pathology, found reduce amyloid-β (Aβ) accumulation tau phosphorylation both wild-type (WT) It also decreases microglial activation increases levels synaptic proteins. review, we examine AD, exploring potential mechanisms action how probiotic strain may aid preventing or treating disease. Furthermore, discuss broader implications improving overall host provide insights into future research directions promising therapy.

Language: Английский

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Multi-Targets: An Unconventional Drug Development Strategy for Alzheimer’s Disease

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: Feb. 9, 2022

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that eventually leads to dementia and death of the patient. Despite enormous amounts resources efforts for AD drug development during last three decades, no effective treatments have been developed can slow or halt progression disease. Currently available drugs treating only improve clinical symptoms temporarily with moderate efficacies. In recent years, scientific community has realized these challenges reconsidered future directions development. The most significant changes in strategy include shifting from amyloid-based targets other targets, such as tau, toward better designs trials. However, still focused on single mechanism target, which conventional Although multifactorial mechanisms and, this basis, multi-target strategies proposed approach not widely recognized accepted by mainstream Here, we emphasize discuss urgent need paradigm shift target multiple either multi-target–directed ligands combination therapy approach. We hope article will increase recognition nature promote shift. believe facilitate successful therapies.

Language: Английский

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Alzheimer’s Disease and Green Tea: Epigallocatechin-3-Gallate as a Modulator of Inflammation and Oxidative Stress

Antioxidants, Journal Year: 2023, Volume and Issue: 12(7), P. 1460 - 1460

Published: July 20, 2023

Alzheimer’s disease (AD) is the most common cause of dementia, characterised by a marked decline both memory and cognition, along with pathophysiological hallmarks including amyloid beta peptide (Aβ) accumulation, tau protein hyperphosphorylation, neuronal loss inflammation in brain. Additionally, oxidative stress caused an imbalance between free radicals antioxidants considered one main risk factors for AD, since it can result protein, lipid nucleic acid damage exacerbate Aβ pathology. To date, there lack successful pharmacological approaches to cure or even ameliorate terrible impact this disease. Due this, dietary compounds antioxidative anti-inflammatory properties acquire special relevance as potential therapeutic agents. In context, green tea, its bioactive compound, epigallocatechin-3-gallate (EGCG), have been targeted plausible option modulation AD. Specifically, EGCG acts antioxidant regulating inflammatory processes involved neurodegeneration such ferroptosis microglia-induced cytotoxicity inducing signalling pathways related survival. Furthermore, reduces hyperphosphorylation aggregation promotes non-amyloidogenic route APP processing, thus preventing formation subsequent accumulation. Taken together, these results suggest that may be suitable candidate search neurodegenerative disorders involving stress,

Language: Английский

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Essential oil of Acorus tatarinowii Schott inhibits neuroinflammation by suppressing NLRP3 inflammasome activation in 3 × Tg-AD transgenic mice

Phytomedicine, Journal Year: 2023, Volume and Issue: 112, P. 154695 - 154695

Published: Feb. 7, 2023

Language: Английский

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GSK3: A potential target and pending issues for treatment of Alzheimer's disease

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(7)

Published: July 1, 2024

Abstract Glycogen synthase kinase‐3 (GSK3), consisting of GSK3α and GSK3β subtypes, is a complex protein kinase that regulates numerous substrates. Research has observed increased GSK3 expression in the brains Alzheimer's disease (AD) patients models. AD neurodegenerative disorder with diverse pathogenesis notable cognitive impairments, characterized by Aβ aggregation excessive tau phosphorylation. This article provides an overview GSK3's structure regulation, extensively analyzing its relationship factors. overactivation disrupts neural growth, development, function. It directly promotes phosphorylation, amyloid precursor (APP) cleavage, leading to formation, or indirectly triggers neuroinflammation oxidative damage. We also summarize preclinical research highlighting inhibition activity as primary therapeutic approach for AD. Finally, pending issues like lack highly specific affinity‐driven inhibitors, are raised expected be addressed future research. In conclusion, represents target treatment, filled hope, challenges, opportunities, obstacles.

Language: Английский

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