BACKGROUND: Tau is a microtubule-associated protein, and variant tau protein is considered to be the key to produce age pigments in Alzheimer’s disease patients. Human synuclein is a main component involved in the formation of amyloidosis in patients with Parkinson’s disease. OBJECTIVE: To summarize the research progress of microtubule-associated substance and its correlation with neurodegenerative diseases. METHODS: A computer-based search of PubMed and Wanfang databases was performed for articles related to microtubule structure and function, microtubule and neurodegenerative diseases associated protein, microtubule-associated substances and their correlation with neurodegenerative diseases published from March 1975 to March 2014. The keywords were “tubulin, Alzheimer disease, Parkinson disease, neurodegeneration” in English and Chinese, respectively. Finally 26 articles were included in result analysis. RESULTS AND CONCLUSION: Microtubule is composed of tubulin and plays an important role as cytoskeleton in cells. In the nervous system, the stability of microtubule system is the foundation of maintaining the nutrient transport between cell bodies and processes. Some researches have confirmed that tubulin is closely related to the key proteins of Parkinson’s disease, Alzheimer’s disease and other neurodegenerative diseases. The aggregation of tau impairs the axonal transport and further influences the morphology and function of neurons. Synuclein can facilitate the polymerization of tubulin into microtubules in early stage of primary cultured neurons. When cells are subject to bad stimulation, abnormal metabolism of microtubule, and its associated substances will lead to the disorder of microtubule system and abnormal accumulation of intracellular substances. The neurons will be eventually degeneration but not apoptosis through unclarified mechanism. Replacement therapy is mainly used in the clinical treatment of neurodegenerative diseases, and there is no patent medicine or treatment method. © 2014, Journal of Clinical Rehabilitative Tissue Engineering Research. All right resurved.