2. Academic Validation
  3. SSK1-Loaded Neurotransmitter-Derived Nanoparticles for Alzheimer's Disease Therapy via Clearance of Senescent Cells

SSK1-Loaded Neurotransmitter-Derived Nanoparticles for Alzheimer's Disease Therapy via Clearance of Senescent Cells

  • Small. 2024 Jun;20(26):e2308574. doi: 10.1002/smll.202308574.
Wenbo Ji 1,  Honglei Zhou 2,  Wendanqi Liang 1 3,  Weicong Zhang 4,  Baofeng Gong 1,  Tong Yin 1,  Jianjian Chu 1,  Jianhua Zhuang 1,  Jian Zhang 5,  Yi Luo 5 6,  Yan Liu 5,  Jie Gao 7,  You Yin 1 8
Affiliations

Affiliations

  • 1 Department of Neurology, Second Afffliated Hospital (Shanghai Changzheng Hospital) of Naval Medical University, Fengyang Road, Huangpu District, Shanghai, 200003, China.
  • 2 Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Changle Road, Qinhuai District, Nanjing, 210006, China.
  • 3 School of Health Science and Engineering, University of Shanghai for Science and Technology, Jungong Road, Yangpu District, Shanghai, 200093, China.
  • 4 School of Pharmacy, University College London, Gower Street, London, W12 8LP, UK.
  • 5 Department of Clinical Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Clinical Pharmacy Innovatton Instttute, Shanghai Jiao Tong University School of Medicine, Kongjiang Road, Yangpu District, Shanghai, 200092, China.
  • 6 New Drug Discovery and Development, Biotheus Inc, Keji 7th Road, TangjiawanTown, Zhuhai, 519080, China.
  • 7 Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Changhai Road, Yangpu District, Shanghai, 200433, China.
  • 8 Department of Neurology, Shanghai East Hospital, School of Medicine, Tongji University, Jimo Road, Pudong New District, Shanghai, 200120, China.
PMID: 38429234 DOI: 10.1002/smll.202308574
Abstract

Age is a significant contributor to the onset of AD. Senolysis has been recently demonstrated to ameliorate aging-associated diseases that showing a great potential in AD therapy. However, due to the presence of BBB, the anti-AD activity of senolytics are significantly diminished. SSK1 is a prodrug that can be activated by β-gal, a lysosomal enzyme commonly upregulated in senescent cells, and thus selectively eliminates senescent cells. Furthermore, the level of β-gal is significantly correlated with conventional AD genes from clinical Sequencing data. SSK1-loaded neurotransmitter -derived lipid nanoparticles are herein developed (SSK1-NPs) that revealing good BBB penetration and bioavailability of in the body. At the brain lesion, SSK1-NP treatment significantly reduces the expression of genes associated with senescence, induced senescent cells elimination, decreased amyloid-beta accumulation, and eventually improve cognitive function of aged AD mice. SSK1-NPs, a novel nanomedicine displaying potent anti-AD activity and excellent safety profile, provides a promising strategy for AD therapy.

Keywords

alzheimer's disease; anti‐ageing; blood‐brain barrier; nanocarrier; senescence.

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