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Nature:中国学者开发阿尔茨海默病颠覆性疗法——短肽通过应力释放,分解tau蛋白纤维
生物世界· 2025-09-16 04:03
Core Viewpoint - Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by memory decline and cognitive impairment, with significant challenges in drug development despite substantial investments from major pharmaceutical companies [3][4]. Group 1: Alzheimer's Disease Overview - Alzheimer's disease is linked to the abnormal accumulation of tau protein and beta-amyloid (Aβ) in the brain, with tau protein aggregation being more closely associated with cognitive symptoms and severity [3]. - Major pharmaceutical companies, including Pfizer, Johnson & Johnson, and Roche, have invested over $10 billion in research for Alzheimer's treatments, but success has been limited [3]. Group 2: Recent Research Findings - A recent study published in Nature by Dr. Ke Hou from UCLA presents a potential strategy to reduce tau protein neurofibrillary tangles (NFTs) in Alzheimer's patients, which may halt disease progression [4]. - The study reveals that D-type peptides can disassemble tau fibrils by assembling into amyloid-like fibers that induce stress release, leading to fiber breakage without the need for enzymatic activity or external energy sources [4][10]. Group 3: Mechanism of Action - The research team explored the mechanism of D-type peptides in disassembling tau protein fibers, identifying D-TLKIVWI as the most effective variant in vitro [6][7]. - D-type peptides assemble into amyloid-like fibers that create torsional stress on tau fibers, resulting in the disruption of local hydrogen bonds and subsequent fiber breakage [8][10]. Group 4: Implications for Treatment - The study highlights the stability, protease resistance, and good biocompatibility of D-type peptides, which can cross the blood-brain barrier without eliciting harmful immune responses [10]. - This research provides a promising new avenue for treating Alzheimer's and other amyloid-related diseases, such as Parkinson's and Huntington's disease, potentially transforming the treatment landscape for neurodegenerative disorders [4][10].
中国博后一作兼通讯Nature论文:为阿尔茨海默病带来颠覆性治疗方法
生物世界· 2025-07-13 03:05
Core Viewpoint - The article discusses a groundbreaking study on tau protein disassembly in Alzheimer's disease, highlighting the potential of D-type peptides as a novel therapeutic strategy to combat neurodegenerative diseases [3][15]. Group 1: Alzheimer's Disease and Tau Protein - Alzheimer's disease (AD) is characterized by cognitive decline and is closely associated with the abnormal aggregation of tau protein and β-amyloid protein [2]. - Tau protein aggregation is more strongly correlated with the cognitive symptoms and severity of Alzheimer's disease compared to β-amyloid [2]. Group 2: Research Findings - A study published in Nature by Dr. Ke Hou from UCLA reveals that D-type peptides can disassemble tau fibrils without the need for enzymatic activity or external energy sources [3][15]. - The research introduces a new paradigm in amyloid protein studies, enhancing understanding of protein aggregation dynamics and inspiring innovative treatment strategies for Alzheimer's and other amyloid-related diseases [3][15]. Group 3: D-type Peptides Advantages - D-type peptides exhibit higher specificity and binding affinity compared to small molecules, with lower immunogenicity and resistance to proteolytic degradation [8]. - Previous studies indicated that D-type peptides could decompose tau protein fibers extracted from Alzheimer's patients and improve behavioral deficits in mouse models [8]. Group 4: Mechanism of Action - The study identified that D-type peptides assemble into amyloid-like fibers, which are essential for disassembling tau protein fibers [12]. - The tension released during the transition from left-handed to right-handed helical structures of these peptides is sufficient to disrupt local hydrogen bonds in tau fibers, leading to their disintegration [13][15]. Group 5: Implications for Treatment - The findings suggest that D-type peptides could revolutionize treatment methods for Alzheimer's disease and provide new tools for tackling other neurodegenerative diseases like Parkinson's and Huntington's disease [15]. - The stability, protease resistance, and good biocompatibility of D-type peptides allow them to cross the blood-brain barrier without eliciting harmful immune responses [15].