Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (2): 424-439.doi: 10.4103/NRR.NRR-D-23-01736

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Nanomaterials-mediated lysosomal regulation: a robust protein-clearance approach for the treatment of Alzheimer’s disease

Mengqi Hao1, 2, #, Jianjian Chu1, #, Tinglin Zhang3, #, Tong Yin1, Yuankai Gu1, Wendanqi Liang1, 2, Wenbo Ji1, Jianhua Zhuang1, Yan Liu4, *, Jie Gao3, *, You Yin1, 5 *   

  1. 1Department of Neurology, Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), Shanghai, China; 2School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China; 3Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China; 4Department of Clinical Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 5Department of Neurology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
  • Online:2025-02-15 Published:2024-06-18
  • Contact: You Yin, PhD, yinyou179@163.com; Jie Gao, PhD, jmsx2021@shu.edu.cn; Yan Liu, PhD, liuyan@shsmu.edu.cn.
  • Supported by:
    The work was supported by the Natural Science Foundation of Shanghai, No. 22ZR147750; Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission, No. 23Y11906600; Shanghai Changzheng Hospital Innovative Clinical Research Project, No. 2020YLCYJ-Y02 (all to YY).

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Abstract: Alzheimer’s disease is a debilitating, progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins, including amyloid plaques and intracellular tau tangles, primarily within the brain. Lysosomes, crucial intracellular organelles responsible for protein degradation, play a key role in maintaining cellular homeostasis. Some studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases, including Alzheimer’s disease. Restoring the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s disease. Currently, the efficacy of drugs in treating Alzheimer’s disease is limited, with major challenges in drug delivery efficiency and targeting. Recently, nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical properties. This review aims to provide a comprehensive overview of recent advances in using nanomaterials (polymeric nanomaterials, nanoemulsions, and carbon-based nanomaterials) to enhance lysosomal function in treating Alzheimer’s disease. This review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal function. In conclusion, this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s disease. The application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.

Key words: Alzheimer’s disease, autophagy dysfunction, lysosomal acidification, lysosomal system, nanomaterials, neurodegenerative diseases