2. Academic Validation
  3. The therapeutic potential of recombinant ANGPTL4 in Parkinson's disease: Evidence from in vivo and in vitro studies

The therapeutic potential of recombinant ANGPTL4 in Parkinson's disease: Evidence from in vivo and in vitro studies

  • Free Radic Biol Med. 2025 Feb 1:227:190-200. doi: 10.1016/j.freeradbiomed.2024.12.009.
Hualing Li 1,  Junjie Wei 2,  Zhiyi Zheng 2,  Rui Wang 2,  Man Qu 3,  Jiangbin Liu 4,  Guotao Lu 5,  Xiaobo Li 6,  Weijuan Gong 7
Affiliations

Affiliations

  • 1 Department of Basic Medicine, Institute of Translational Medicine, Medical College, Yangzhou University, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, China.
  • 2 Department of Basic Medicine, Institute of Translational Medicine, Medical College, Yangzhou University, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, China.
  • 3 School of Nursing and Public Health, Yangzhou University, China.
  • 4 Department of Neurology, Affiliated Hospital of Yangzhou University, China.
  • 5 Department of Gastroenterology, Affiliated Hospital of Yangzhou University, China. Electronic address: gtlu@yzu.edu.cn.
  • 6 Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, China. Electronic address: xiaoboli@yzu.edu.cn.
  • 7 Department of Basic Medicine, Institute of Translational Medicine, Medical College, Yangzhou University, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, China. Electronic address: wjgong@yzu.edu.cn.
PMID: 39643133 DOI: 10.1016/j.freeradbiomed.2024.12.009
Abstract

Background: The established body of knowledge attests to the pivotal influence of ANGPTL4 on lipid metabolism and vascular biology. Nevertheless, its potential implication in neurodegenerative disease remains to be fully characterized.

Methods: The present investigation delves into the involvement of ANGPTL4 in the pathological progression of PD, both in vitro and in vivo. PD models were induced by intraperitoneal administration of MPTP and LPS in WT and ANGPTL4-/- mice. Additionally, rANGPTL4 was administered intravenously via the tail. Primary microglia cells cultured from the SNpc and Str regions of brains were exposed to LPS to induce neuroinflammation.

Results: The observations unveiled that ANGPTL4 deficiency exacerbated behavioral aberrations, intensified dopaminergic neuron loss, and stimulated microglial activation along with p21-dependent senescence. There was an elevation in the expression of proinflammatory cytokines in the PD model. Furthermore, the administration of rANGPTL4 protein reversed the observed phenotypes in ANGPTL4-/- mice, a phenomenon further validated in LPS-induced cells. Clinical specimens also manifested diminished levels of ANGPTL4 expression in PD patients. ANGPTL4 demonstrated the ability to alleviate neuroinflammation by suppressing EIF2-JNK-mediated ER stress and eliminating senescent cells.

Conclusion: Our findings posit a salutary role for ANGPTL4 in counteracting PD, rendering it a prospective therapeutic target for the development of innovative drugs aimed at treating neuroinflammation-associated neurological diseases, including PD.

Keywords

ANGPTL4; EIF2-JNK pathway; Microglia; PD; p21 dependent senescence.

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