In Vitro and in Vivo Studies of Chlorella Bioactive Peptides on Improving Neurotoxic Substances-Induced Neuronal Injury / 以活體外及活體試驗探討小球藻生物活性胜肽對於改善神經毒性物質所誘導神經細胞損傷之機制

碩士 / 輔仁大學 / 生命科學系碩士班 / 106 / Alzheimer's disease (AD) is one of neurodegenerative disorders occurring in the brain and is the typical type of senile dementia (approximately 60-80%). The early symptom is usually associated with the increase of oxidative stress and inflammatory factors, following the neuritic beta-amyloid (Aβ), plaques of tau protein and the intraneuronal accumulation of neurofibrillary tangles (NFTs) in the brain. As the disease advances, it includes neuron apoptosis and loss combined with cerebral atrophy leading to a serious cognitive impairment and long-term memory loss. Chlorella sp., also known as Chlorococcum, contains proteins, amino acids, peptides, carbohydrate, lipids, vitamins and carotenoids. In recent years, Chlorella extracts have been widely studied as prevention or treatment in many neurodegenerative diseases. In our study, we propose to elucidate the neuroprotective effects of Chlorella pyrenoidosa short-chain peptides (CPPs) <1 kDa, 1-3 kDa, 3-10 kDa and >10 kDa, there have been proven as anti-inflammatory or anti-oxidant, and find out the pharmacological activities and its mechanism of action in the early and late inflammatory phase of Alzheimer's disease model in vitro. Our results showed that the 1-3 kDa and 3-10 kDa molecular weight of chlorella peptide could elevate the survival rate of N2A cell induced by Aβ1-42 or L-Glutamic acid. Moreover, it reduced both tau protein and amyloid precursor protein (APP) expression in N2A cell, also prevented the neuron from progressive cell damage by suppressing cytokines in medium, such as PGE2, iNOS, IL-6, TNF-α, COX-2, IL-1β released from LPS-induced microglial or macrophage, and TGF-β1, NFκB mRNA expression that produced by themselves. Further, we find out those peptides could improve spatial cognition and learning memory in Aβ1-42-induced degenerative Alzheimer's disease model in vivo by oral-feeding 1-3 kDa or 3-10 kDa molecular weight of chlorella peptide as prevention, and we also observed that it decreased the cell loss ratio on CA1-CA3 region of hippocampus. Based on our above findings, CPPs have obvious efficacy in preventing Alzheimer's disease, and the possible mechanisms are closely related to specific molecular weight of chlorella functional peptides and their anti-inflammatory effect.

Identiferoai:union.ndltd.org:TW/106FJU00105007
Date January 2018
CreatorsWANG, SHU-MEI, 王舒眉
ContributorsSu, Ruey-Chih, Chuu, Jiunn-Jye, 蘇睿智, 褚俊傑
Source SetsNational Digital Library of Theses and Dissertations in Taiwan
Languagezh-TW
Detected LanguageEnglish
Type學位論文 ; thesis
Format105

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