The Study of Postmortem Human Synaptosomes for Understanding Alzheimer’s Disease and Other Neurological Disorders: A Review

被引:36
作者
Jhou J.-F. [1 ]
Tai H.-C. [1 ]
机构
[1] Department of Chemistry, National Taiwan University, Taipei
关键词
Brain bank; Neurochemistry; Neurodegeneration; Neuron; Subcellular fractionation; Synapse;
D O I
10.1007/s40120-017-0070-z
中图分类号
学科分类号
摘要
Synaptic dysfunction is thought to play important roles in the pathophysiology of many neurological diseases, including Alzheimer’s disease, Parkinson’s disease, and schizophrenia. Over the past few decades, there have been systematic efforts to collect postmortem brain tissues via autopsies, leading to the establishment of dozens of human brain banks around the world. From cryopreserved human brain tissues, it is possible to isolate detached-and-resealed synaptic terminals termed synaptosomes, which remain metabolically and enzymatically active. Synaptosomes have become important model systems for studying human synaptic functions, being much more accessible than ex vivo brain slices or primary neuronal cultures. Here we review recent advances in the establishment of human brain banks, the isolation of synaptosomes, their biological activities, and various analytical techniques for investigating their biochemical and ultrastructural properties. There are unique insights to be gained by directly examining human synaptosomes, which cannot be substituted by animal models. We will also discuss how human synaptosome research has contributed to better understanding of neurological disorders, especially Alzheimer’s disease. © 2017, The Author(s).
引用
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页码:57 / 68
页数:11
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共 93 条
  • [11] Whittaker V.P., Thirty years of synaptosome research, J Neurocytol, 22, pp. 735-742, (1993)
  • [12] Bermejo M.K., Milenkovic M., Salahpour A., Ramsey A.J., Preparation of synaptic plasma membrane and postsynaptic density proteins using a discontinuous sucrose gradient, J Vis Exp, (2014)
  • [13] Franklin W., Taglialatela G., A method to determine insulin responsiveness in synaptosomes isolated from frozen brain tissue, J Neurosci Methods, 261, pp. 128-134, (2016)
  • [14] Marcelli S., Ficulle E., Iannuzzi F., Kovari E., Nistico R., Feligioni M., Targeting SUMO-1ylation contrasts synaptic dysfunction in a mouse model of Alzheimer’s disease, Mol Neurobiol, (2016)
  • [15] Kretzschmar H., Brain banking: opportunities, challenges and meaning for the future, Nat Rev Neurosci, 10, pp. 70-78, (2009)
  • [16] Bell J.E., Alafuzoff I., Al-Sarraj S., Arzberger T., Bogdanovic N., Budka H., Et al., Management of a twenty-first century brain bank: experience in the BrainNet Europe consortium, Acta Neuropathol, 115, pp. 497-507, (2008)
  • [17] Nichols L., Freund M., Ng C., Kau A., Parisi M., Taylor A., Et al., The National Institutes of Health Neurobiobank: a federated national network of human brain and tissue repositories, Biol Psychiatry, 75, pp. e21-e22, (2014)
  • [18] Glenner G.G., Wong C.W., Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein, Biochem Biophys Res Commun, 120, pp. 885-890, (1984)
  • [19] Spillantini M.G., Schmidt M.L., Lee V.M.-Y., Trojanowski J.Q., Jakes R., Goedert M., Synuclein in Lewy bodies, Nature, 388, pp. 839-840, (1997)
  • [20] Poorkaj P., Bird T.D., Wijsman E., Nemens E., Garruto R.M., Anderson L., Et al., Tau is a candidate gene for chromosome 17 frontotemporal dementia, Ann Neurol, 43, pp. 815-825, (1998)