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核心技术专利：CN118964589B侵权必究
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精髓协同作用：同时给予综合应激反应抑制剂和 BACE1 和/或 BACE2 激活剂，作为阿尔茨海默病的最佳治疗策略。

Quintessential Synergy: Concurrent Transient Administration of Integrated Stress Response Inhibitors and BACE1 and/or BACE2 Activators as the Optimal Therapeutic Strategy for Alzheimer's Disease.

机构信息

Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.

Division of Molecular Medicine, Children's Hospital, Boston, MA 02115, USA.

出版信息

Int J Mol Sci. 2024 Sep 13;25(18):9913. doi: 10.3390/ijms25189913.

DOI:10.3390/ijms25189913
PMID:39337400
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11432332/
Abstract

The present study analyzes two potential therapeutic approaches for Alzheimer's disease (AD). One is the suppression of the neuronal integrated stress response (ISR). Another is the targeted degradation of intraneuronal amyloid-beta (Aβ) via the activation of BACE1 (Beta-site Aβ-protein-precursor Cleaving Enzyme) and/or BACE2. Both approaches are rational. Both are promising. Both have substantial intrinsic limitations. However, when combined in a carefully orchestrated manner into a composite therapy they display a prototypical synergy and constitute the apparently optimal, potentially most effective therapeutic strategy for AD.

摘要

本研究分析了两种潜在的阿尔茨海默病（AD）治疗方法。一种是抑制神经元整合应激反应（ISR）。另一种是通过激活 BACE1（β-位淀粉样前体蛋白裂解酶 1）和/或 BACE2，靶向降解神经元内的淀粉样β（Aβ）。这两种方法都是合理的。这两种方法都是有前途的。这两种方法都有实质性的内在局限性。然而，当以一种精心协调的方式组合成一种综合疗法时，它们表现出典型的协同作用，构成了 AD 显然最佳、最有效的潜在治疗策略。

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引用本文的文献

[1]
Alzheimer's Is a Multiform Disease of Sustained Neuronal Integrated Stress Response Driven by the C99 Fragment Generated Independently of AβPP; Proteolytic Production of Aβ Is Suppressed in AD-Affected Neurons: Evolution of a Theory.

Int J Mol Sci. 2025-4-29

[2]
Production of Amyloid-β in the Aβ-Protein-Precursor Proteolytic Pathway Is Discontinued or Severely Suppressed in Alzheimer's Disease-Affected Neurons: Contesting the 'Obvious'.

Genes (Basel). 2025-1-2

本文引用的文献

[1]
ACH2.0/E, the Consolidated Theory of Conventional and Unconventional Alzheimer's Disease: Origins, Progression, and Therapeutic Strategies.

Int J Mol Sci. 2024-5-30

[2]
On the Inadequacy of the Current Transgenic Animal Models of Alzheimer's Disease: The Path Forward.

Int J Mol Sci. 2024-3-4

[3]
Next Generation Therapeutic Strategy for Treatment and Prevention of Alzheimer's Disease and Aging-Associated Cognitive Decline: Transient, Once-in-a-Lifetime-Only Depletion of Intraneuronal Aβ (Aβ) by Its Targeted Degradation via Augmentation of Intra-Aβ-Cleaving Activities of BACE1 and/or BACE2.

Int J Mol Sci. 2023-12-18

[4]
Principles of Design of Clinical Trials for Prevention and Treatment of Alzheimer's Disease and Aging-Associated Cognitive Decline in the ACH2.0 Perspective: Potential Outcomes, Challenges, and Solutions.

J Alzheimers Dis Rep. 2023-8-28

[5]
Evidence supportive of a bacterial component in the etiology for Alzheimer's disease and for a temporal-spatial development of a pathogenic microbiome in the brain.

Front Cell Infect Microbiol. 2023

[6]
MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer's disease.

Science. 2023-9-15

[7]
Alzheimer's disease as a viral disease: Revisiting the infectious hypothesis.

Ageing Res Rev. 2023-11

[8]
Hospital-Diagnosed Infections, Autoimmune Diseases, and Subsequent Dementia Incidence.

JAMA Netw Open. 2023-9-5

[9]
The Amyloid Cascade Hypothesis 2.0 for Alzheimer's Disease and Aging-Associated Cognitive Decline: From Molecular Basis to Effective Therapy.

Int J Mol Sci. 2023-7-31

[10]
Clinical evidence of human pathogens implicated in Alzheimer's disease pathology and the therapeutic efficacy of antimicrobials: an overview.

Transl Neurodegener. 2023-7-26

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