Integrin α5β1 Activation by PHSRN Peptide Elicits Neuroprotection and Functional Recovery in Parkinson's Disease Mice.
Integrin α5β1 Activation by PHSRN Peptide Elicits Neuroprotection and Functional Recovery in Parkinson's Disease Mice.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Kaohsiung, TW · Author affiliation
Graduate Institute of Medicine, College of Medicine, I-Shou University, Kaohsiung City 824005, Taiwan.Location evidence
Taipei, TW · Author affiliation
Division of Experimental Surgery Center, Department of Surgery, Tri-Service General Hospital, National Defense Medical University, Taipei 114201, Taiwan.Location evidence
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Original abstract
Parkinson's disease (PD) is characterized by progressive dopaminergic neurodegeneration driven by oxidative stress, mitochondrial dysfunction, synaptic loss, and impaired neurotrophic signaling; however, the role of integrin α5β1 in neuronal vulnerability remains unclear. Here, the data show that rotenone-induced stress reduces integrin α5 expression in a dose- and time-dependent manner, leading to increased ROS accumulation, glutathione imbalance, synaptic degeneration, senescence-like β-gal activity, and apoptosis, whereas integrin α5 knockdown further exacerbates these deficits, supporting a protective role of α5β1. In contrast, treatment with the fibronectin-derived α5β1-activating peptide Ac-PHSRN-NH2 restores integrin signaling by engaging the FAK-PI3K-AKT/ERK cascade and NRF2-mediated antioxidant responses, thereby reducing oxidative stress, suppressing cell death, and improving redox homeostasis. Moreover, PHSRN enhances NGF and BDNF levels, preserves synaptic integrity, and promotes dopaminergic neuronal activity and dopamine release. Consistently, in MPTP-lesioned mice, PHSRN preserves nigral TH-positive neurons, reduces apoptosis, restores neurotrophic support, and improves motor function. Collectively, these findings identify integrin α5β1 as a critical protective axis and support PHSRN as a potential disease-modifying therapeutic strategy for PD.