Advances and Challenges in Gene Therapy for Alzheimer’s Disease DOI
Fabiana Morroni, Antonella Caccamo

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 101(s1), P. S417 - S431

Published: Oct. 18, 2024

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and behavioral impairments. Despite extensive research efforts, effective treatment options for AD remain limited. Recently, gene therapy has emerged as promising avenue targeted intervention in the pathogenesis of AD. This review will provide an overview clinical preclinical studies where techniques have been utilized context AD, highlighting their potential novel therapeutic strategies. While challenges remain, ongoing technological advancement continue to enhance personalized approach

Language: Английский

BACE1 Inhibitors for Alzheimer’s Disease: Current Challenges and Future Perspectives DOI
Judite R.M. Coimbra, Rosa Resende, José B.A. Custódio

et al.

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 101(s1), P. S53 - S78

Published: June 25, 2024

Disease-modifying therapies (DMT) for Alzheimer’s disease (AD) are highly longed-for. In this quest, anti-amyloid take center stage supported by genetic facts that highlight an imbalance between production and clearance of amyloid-β peptide (Aβ) in AD patients. Indeed, evidence from basic research, human biomarker studies, suggests the accumulation Aβ as a driver pathogenesis progression. The aspartic protease β-site AβPP cleaving enzyme (BACE1) is initiator production. Underpinning critical role BACE1 pathophysiology elevated concentration activity observed brain body fluids Therefore, prime drug target reducing levels early AD. Small-molecule inhibitors have been extensively developed last 20 years. However, clinical trials with these molecules discontinued futility or safety reasons. Most adverse side effects were due to other proteases cross-inhibition, including homologue BACE2, mechanism-based toxicity since has substrates important roles synaptic plasticity homeostasis besides protein precursor (AβPP). Despite setbacks, persists well-validated therapeutic which specific inhibitor high substrate selectivity may yet be found. review we provide overview evolution design pinpointing reached advanced phases liabilities precluded adequate trial effects. Finally, ponder on challenges must overcome achieve success.

Language: Английский

Citations

5
Development of novel BACE1 inhibitors with a hydroxyproline-derived N-amidinopyrrolidine scaffold DOI
Kazuya Kobayashi,

Chinami Taniguchi,

Maria Tanaka

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 118086 - 118086

Published: Jan. 1, 2025

Language: Английский

Citations

0
Exploring 4-quinolone-3-carboxamide derivatives: A versatile framework for emerging biological applications DOI
Joana Andrade, Thiago Mota do Vale,

R. Gomes

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 157, P. 108240 - 108240

Published: Feb. 3, 2025

Language: Английский

Citations

0
Structure-based identification of potent modulators from Centella asiatica targeting BACE-1 DOI Creative Commons
Armin Sultana, Joohan Woo

Heliyon, Journal Year: 2025, Volume and Issue: unknown, P. e42652 - e42652

Published: Feb. 1, 2025

Language: Английский

Citations

0
Anti-amyloid β hydrophobic peptides in Alzheimer’s disease: biomarkers and therapeutic potential DOI Creative Commons
Carlos Gutiérrez‐Merino

Exploration of neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Intracellular amyloid β oligomers (AβOs) have been linked to Alzheimer’s disease (AD) pathogenesis and the neuronal damage in this neurodegenerative disease. Calmodulin, which binds AβO with very high affinity, plays a pivotal role Aβ-induced neurotoxicity has used as model template protein for design of AβO-antagonist peptides. The hydrophobic amino acid residues COOH-terminus domain Aβ play leading its interaction intracellular proteins that bind affinity. This review focuses on Aβ-antagonist peptides their endogenous production brain, highlighting proteasome major source type It is emphasized level these neuropeptides undergoes significant changes brain AD patients relative age-matched healthy individuals. concluded may become helpful biomarkers evaluation risk onset sporadic and/or prognosis AD. In addition, seem priori good candidates development novel therapies, could be combination other drug-based therapies. Future perspectives limitations use clinical management are briefly discussed.

Language: Английский

Citations

0
The potential utility of arterial spin labeling in predicting brain amyloidosis DOI
Kimia Kazemzadeh,

Nahid Gharib Naseri,

Mahsa Mombeini

et al.

Journal of Clinical Neuroscience, Journal Year: 2025, Volume and Issue: 137, P. 111248 - 111248

Published: May 5, 2025

Language: Английский

Citations

0
Microorganism-Derived Molecules as Enzyme Inhibitors to Target Alzheimer’s Diseases Pathways DOI Creative Commons
Thi Hanh Nguyen, San‐Lang Wang, Van Bon Nguyen

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(4), P. 580 - 580

Published: April 12, 2023

Alzheimer’s disease (AD) is the most common form of dementia. It increases risk other serious diseases and causes a huge impact on individuals, families, socioeconomics. AD complex multifactorial disease, current pharmacological therapies are largely based inhibition enzymes involved in pathogenesis AD. Natural enzyme inhibitors potential sources for targeting treatment mainly collected from plants, marine organisms, or microorganisms. In particular, microbial have many advantages compared to sources. While several reviews been reported, these previous focused presenting discussing general theory overviewing various sources, such as chemical synthesis, while only few regarding against available. Currently, multi-targeted drug investigation new trend However, there no review that has comprehensively discussed kinds source. This extensively addresses above-mentioned aspect simultaneously updates provides more comprehensive view targets The emerging using silico studies discover drugs concerning microorganisms perspectives further experimental also covered here.

Language: Английский

Citations

9
Omaveloxolone ameliorates cognitive dysfunction in APP/PS1 mice by stabilizing the STAT3 pathway DOI Creative Commons
Xiaolin Cui, Shuai Zong,

Wenao Song

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 335, P. 122261 - 122261

Published: Nov. 10, 2023

To determine the availability and potential molecular mechanisms underlying therapeutic effect of omaveloxolone (RTA408) on Alzheimer's Disease (AD).This study employed network pharmacology to assess feasibility drug treatment AD. cognitive status emotional state APPswe/PS1dE9 (APP/PS1) mice after RTA408 treatment, three classical behavioral experiments (water maze, Y-maze, open field test) were conducted. Immunofluorescence immunohistochemical staining utilized evaluate hippocampal neuronal amyloid (Aβ) deposition in mice. RNA-seq transcription factor prediction analyses performed explore regulating effects RTA408. Molecular docking was predict direct targets. validate these mechanisms, quantitative reverse PCR (qRT-PCR), Western blotting, immunofluorescence two instrumental cell lines, i.e., mouse cells (HT22) microglia (BV2).RTA408 revealed with capability reduce Aβ plaque restore damaged neurons region APP/PS1 mice, ultimately leading an improvement function. This beneficial achieved by balancing STAT3 pathway. Specifically, facilitated activations both STAT3/OXR1 NRF2/ARE axes, thereby enhancing compromised resistance oxidative stress. inhibited NFκB/IL6/STAT3 pathway, effectively countering neuroinflammation triggered microglial activation.RTA408 is promising AD based preclinical data.

Language: Английский

Citations

7
Combination strategy employing BACE1 inhibitor and memantine to boost cognitive benefits in Alzheimer’s disease therapy DOI
Abu Md Mamun Tarif,

Hasi Huhe,

Masuo Ohno

et al.

Psychopharmacology, Journal Year: 2024, Volume and Issue: 241(5), P. 975 - 986

Published: Jan. 10, 2024

Language: Английский

Citations

2
Passive Anti-Amyloid Beta Immunotherapies in Alzheimer’s Disease: From Mechanisms to Therapeutic Impact DOI Creative Commons
Thomas Gabriel Schreiner, Cristina Croitoru,

Diana Nicoleta Hodorog

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(5), P. 1096 - 1096

Published: May 15, 2024

Alzheimer’s disease, the most common type of dementia worldwide, lacks effective disease-modifying therapies despite significant research efforts. Passive anti-amyloid immunotherapies represent a promising avenue for disease treatment by targeting amyloid-beta peptide, key pathological hallmark disease. This approach utilizes monoclonal antibodies designed to specifically bind amyloid beta, facilitating its clearance from brain. review offers an original and critical analysis exploring several aspects. Firstly, mechanisms action these are reviewed, focusing on their ability promote Aβ degradation enhance efflux central nervous system. Subsequently, extensive history clinical trials involving is presented, initial efforts using first-generation molecules leading mixed results recent clinically approved drugs. Along with undeniable progress, authors also highlight pitfalls this offer balanced perspective topic. Finally, based potential limitations, future directions therapeutic strategy emphasized.

Language: Английский

Citations

2