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Recent Advancements in Strategies for Abnormal Protein Clearance in Alzheimer's Disease

期刊

MINI-REVIEWS IN MEDICINAL CHEMISTRY
卷 22, 期 17, 页码 2260-2270

出版社

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1389557522666220214092824

关键词

Alzheimer's disease; amyloid; tau; abnormal protein; clearance strategies; immunotherapy; nanomedicine

资金

  1. Innovative Clinical Research Project of Changzheng Hospital [2020YLCYJ-Y02]
  2. Special Military Medical Service Project of Changzheng Hospital [2020CZWJFW12]
  3. Science and Technology Support Project in Biomedical Field of Shanghai Science and Technology Commission [19441907500]
  4. Naval Medical University Military Medicine Innovation Special Project [2017JS07]
  5. Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission [17411950104]
  6. Natural Science Foundation of Shanghai [22ZR147750]
  7. National Natural Science Foundation of China [81771964, 82072051]

向作者/读者索取更多资源

Alzheimer's disease is a complex neurodegenerative disease characterized by the accumulation of A beta and tau proteins, leading to an imbalance in clearance and production rates. Current therapeutic strategies have limited effectiveness, but recent advances in immunotherapies and nanomedicines targeting these abnormal proteins may represent a crucial breakthrough.
Alzheimer's disease (AD) is an intricate neurodegenerative disease with chronic and progressive development whose typical neuropathological features encompass senile plaques and neurofibrillary tangles, respectively formed by the extracellular deposition of amyloid-beta (A beta) and the intracellular accumulation of hyperphosphorylated tau protein in the brain, particularly in limbic and cortical regions. The pathological changes are considered to be caused by the loss of A beta and tau protein clearance mechanisms under pathological conditions, which leads to an imbalance between the rates of clearance and production. Consequently, the main strategies for treating AD aim to reduce the production of A beta and hyperphosphorylated tau protein in the brain, inhibit their accumulation, or accelerate their clearance. Although drugs utilizing these therapeutic strategies have been studied successively, their therapeutic effects have generally been less than ideal. Fortunately, recent advances have been made in clearance strategies for these abnormally expressed proteins, including immunotherapies and nanomedicines targeting A beta or tau, which could represent an important breakthrough for treating AD. Here, we review recent development of the strategies for the removal of abnormal proteins and provide new ideas and methods for treating AD.

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