實驗室名稱：神經退化標誌研究室
主持人：林詠峯老師
許多先進國家或地區包括台灣，因人口老化和環境污染等問題，導致神經退化性失智如阿茲海默症(Alzheimer's disease, AD)的影響日益嚴重。根據統計，全台目前的失智人口約百分之一，估計二十年後會超過百分之三。已知類澱粉胜肽的產生以致在腦中堆積是這類神經退化的主因，因此本研究室利用細胞和小鼠等實驗模型，以及檢測臨床病人血液中成份，探討神經退化中與類澱粉前驅蛋白(amyloid precursor protein, APP)的囊泡運輸以及轉譯後修飾(post-translational modification, PTM)相關之致病機轉、生物標誌、以及使用醣苷神經鞘醯胺類(gangliosides)藥物、人參廢料萃取物等之療效和安全性評估，研究成果可作為將來臨床試驗的準備；不僅可以促進病人福祉，也減低家屬和社會的負擔。
Figure 1. The microtubule-based vesicle transport machinery containing motor proteins, namely dynein/dynactin and kinesin, and adaptors, AHI1 and HAP1, is vital for neuronal survival by delivering neurotrophic cargos such as APP and Trk. Gangliosides may surround APP and other neurotrophic receptors and affect their vesicular transport via HAP1/AHI1-interacting proteins. The level and modification of these proteins could serve as biomarkers for early diagnosis and treatment of neurodegenerative diseases.
Figure 2. Proposed reactions of acrolein-Aβ adduct formation and degradation in correlation with metabolic disturbance and neurodegeneration.
References
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- Serum levels of 4-hydroxynonenal adducts and responding autoantibodies correlate with the pathogenesis from hyperglycemia to Alzheimer’s disease. Clin Biochem 2022 101:26-34
- Protective evaluation of compounds extracted from root of Rhodiola rosea L. against methylglyoxal-induced toxicity in a neuronal cell line. Molecules 2020 25(12):2801
- Alzheimer’s disease and diabetes: insulin signaling as the bridge linking two pathologies. Mol Neurobiol 2020 57(4):1966-1977 (Review article)
- Reduction of AHI1 in the serum of Taiwanese with probable Alzheimer’s disease. Clin Biochem 2020 76:24-30
- Expression of AHI1 rescues amyloidogenic pathology in Alzheimer’s disease model cells. Mol Neurobiol 2019 56(11):7572-7582
- Ganglioside Hp-s1 analogue inhibits amyloidogenic toxicity in Alzheimer’s disease model cells. ACS Chem Neurosci 2019 10:528-536
- Elevated IgM against Nε-(Carboxyethyl)lysine-modified Apolipoprotein A1 peptide 141-147 in Taiwanese with Alzheimer’s disease. Clin Biochem 2018 56:75-82