Neuroprotective Peptide Mechanisms

# Introduction Neuroprotective peptides represent a promising therapeutic strategy for the prevention and treatment of various neurodegenerative disorders, including Alzheimer's disease, ischemic stroke, and others. They exert their neuroprotective effects via multiple mechanisms, including the regulation of signaling pathways, promotion of neuronal survival, reduction of neuroinflammation, and protection against oxidative stress [1][3][4][5][6][8][9][10]. This article will detail the neuroprotective mechanisms of peptides, based on the evidence from preclinical and clinical studies. # Preclinical Research ## Apelin-13 and the Keap1/Nrf2 Signaling Pathway In a preclinical study, Guo et al. found that Apelin-13, a neuroprotective peptide, can attenuate blood-brain barrier dysfunction following intracerebral hemorrhage [1]. The protective effect of Apelin-13 is mediated through the Kelch-like ECH-associated protein 1/Nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) signaling pathway. This pathway plays an essential role in cellular protection against oxidative stress and inflammation [1]. ## Tenuigenin and MAP2K1 Targeting Another peptide, Tenuigenin, has shown potential in ameliorating Alzheimer's disease by targeting MAP2K1, a key component of the MAPK signaling pathway involved in cell proliferation, differentiation, and apoptosis [3]. This evidence was derived from network pharmacology and experimental validation [3]. ## Neuroprotective Effects of Cratoxylum formosum Leaf Extract Palachai et al. reported the neuroprotective effects of Cratoxylum formosum leaf extract against β-amyloid-induced injury in human neuroblastoma SH-SY5Y cells [4]. β-amyloid is a peptide that forms plaques in the brains of Alzheimer's patients, leading to neuronal damage [4]. # Clinical Evidence Direct human evidence on the neuroprotective mechanisms of peptides is not present in the provided citations. # Safety and Limitations While the studies mentioned provide promising evidence on the neuroprotective effects of peptides, there are several limitations. For one, most of the current research is preclinical, conducted in vitro or in animal models, which may not fully replicate the complexity of human neurodegenerative disorders. Furthermore, the safety profile of these peptides, including potential side effects and interactions with other drugs, needs to be thoroughly evaluated in human clinical trials. # Key Takeaways Neuroprotective peptides hold significant potential for the prevention and treatment of neurodegenerative diseases. They work through various mechanisms, including the regulation of key signaling pathways, reduction of neuroinflammation, and protection against oxidative stress. Notable peptides include Apelin-13, which acts via the Keap1/Nrf2 signaling pathway, and Tenuigenin, which targets MAP2K1. The leaf extract of Cratoxylum formosum has also demonstrated neuroprotective effects against β-amyloid-induced injury. However, more comprehensive clinical trials are required to validate these findings and assess the safety profile of these peptides in humans.