Tau蛋白对阿尔茨海默病线粒体形态分布及功能的影响机制的研究进展_West China Medical Journal

Authors：

 李夏春

三峡大学医学院病理生理教研室（湖北宜昌，443002）;

Corresponding author：

Keywords：

Tau蛋白; 线粒体; 分布; 形态; 功能

DOI：

10.7507/1002-0179.20140484

Video：

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过度磷酸化的微管结合Tau蛋白是阿尔茨海默病患者神经元内神经原纤维缠结的主要成分，但适度磷酸化的Tau蛋白又是参与微管组装和维持微管稳定的重要骨架蛋白。近年来，Tau蛋白对线粒体的转运、分布和形态及功能的影响受到广泛研究。现对上述研究进展作一综述。

Citation： 李夏春. Tau蛋白对阿尔茨海默病线粒体形态分布及功能的影响机制的研究进展. West China Medical Journal, 2014, 29(8): 1583-1585. doi: 10.7507/1002-0179.20140484 Copy

1.	Hirai K, Aliev G, Nunomura A, et al. Mitochondrial abnormalities in Alzheimer's disease[J]. J Neurosci, 2001, 21(9):3017-3023.
2.	Wang X, Su B, Fujioka H, et al. Dynamin-like protein 1 reduction underlies mitochondrial morphology and distribution abnormalities in fibroblasts from sporadic Alzheimer's disease patients[J]. Am J Pathol, 2008, 173(2):470-482.
3.	Wei Y, Qu MH, Wang XS, et al. Binding to the minor groove of the double-strand, tau protein prevents DNA from damage by peroxidation[J]. PLoS ONE, 2008, 3(7):e2600.
4.	Manczak M, Reddy PH. Abnormal interaction between the mitochondrial fission protein Drp1 and hyperphosphorylated Tau in Alzheimer's disease neurons:implications for mitochondrial dysfunction and neuronal damage[J]. Hum Mol Genet, 2012, 21(11):2538-2547.
5.	Manczak M, Sesaki H, Kageyama Y, et al. Dynamin-related protein 1 heterozygote knockout mice do not have synaptic and mitochondrial deficiencies[J]. Biochim Biophys Acta, 2012, 1822(6):862-874.
6.	Jellinger KA. Challenges in neuronal apoptosis[J]. Curr Alzheimer Res, 2006, 3(4):377-391.
7.	DuBoff B, Gotz J, Feany MB. Tau promotes neurodegeneration via DRP1 mislocalization in vivo[J]. Neuron, 2012, 75, 618-632.
8.	Schulz KL, Eckert A, Rhein V, et al. A new link to mitochondrial impairment in Tauopathies[J]. Mol Neurobiol, 2012, 46(1):205-216.
9.	Kopeikina KJ, Carlson GA, Pitstick R, et al. Tau accumulation causes mitochondrial distribution deficits in neurons in a mouse model of Tauopathy and in human Alzheimer's disease brain[J]. Am J Pathol, 2011, 179(4):2071-2082.
10.	Michal C, Dzhamilja S, Mailis L, et al. Principles of the mitochondrial fusion and fission cycle in neurons[J]. J Cell Sci, 2013, 126(10):2187-2197.
11.	Dixit R, Ross JL, Goldman YE, et al. Differential regulation of dynein and kinesin motor proteins by Tau[J]. Science, 2008, 319(5866):1086-1089.
12.	Stoothoff W, Jones PB, Spires-Jones TL. Differential effect of three-repeat and four-repeat Tau on mitochondrial axonal transport[J]. J Neurochem, 2009, 111(2):417-427.
13.	McVicker DP, Chrin LR, Berger CL. The nucleotide-binding state of microtubules modulates kinesin processivity and the ability of Tau to inhibit kinesin-mediated transport[J]. J Biol Chem, 2011, 286(50):42873-42880.
14.	Tatebayashi Y, Haque N, Tung YC, et al. Role of Tau phosphorylation by glycogen synthase kinase-3beta in the regulation of organelle transport[J]. J Cell Sci, 2004, 117(9):1653-1663.
15.	Shahpasand K, Uemura I, Saito T, et al. Regulation of mitochondrial transport and inter-microtubule spacing by Tau phosphorylation at the sites hyperphosphorylated in Alzheimer's disease[J]. J Neurosci, 2012, 32(7):2430-2441.
16.	Kanaan NM, Morfini G, Pigino G, et al. Phosphorylation in the amino terminus of Tau prevents inhibition of anterograde axonal transport[J]. Neurobiol Aging, 2012, 33(4):826.e15-826.e30.
17.	Quintanilla RA, Matthews-Roberson TA, Dolan PJ, et al. Caspase-cleaved Tau expression induces mitochondrial dysfunction in immortalized cortical neurons:implications for the pathogenesis of Alzheimer disease[J]. J Biol Chem, 2009, 284(28):18754-18766.
18.	Amadoro G, Corsetti V, Stringaro A,et al. A NH2 Tau fragment targets neuronal mitochondria at AD synapses:possible implications for neurodegeneration[J]. J Alzheimers Dis, 2010, 21(2):445-470.
19.	Rhein V, Song X, Wiesner A, et al. Amyloid-beta and Tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer's disease mice[J]. Proc Natl Acad Sci USA, 2009, 106(47):20057-20062.
20.	Atlante A, Amadoro G, Bobba A, et al. A peptide containing residues 26-44 of Tau protein impairs mitochondrial oxidative phosphorylation acting at the level of the adenine nucleotide translocator[J]. Biochim Biophys Acta, 2008, 1777(10):1289-1300.
21.	Van der Jeugd A, Ahmed T, Burnouf S, et al. Hippocampal Tauopathy in Tau transgenic mice coincides with impaired hippocampus-dependent learning and memory, and attenuated late-phase long-term depression of synaptic transmission[J]. Neurobiol. Learn Mem, 2011, 95:296-304.
22.	Manczak M, Hemachandra Reddy P. Abnormal interaction of VDAC1 with amyloid beta and phosphorylated Tau causes mitochondrial dysfunction in Alzheimer's disease[J]. Hum Mol Genet, 2012, 21(23):5131-5146.
23.	Merkwirth C, Martinelli P, Korwitz A, et al. Loss of prohibitin membrane scaffolds impairs mitochondrial architecture and leads to Tau hyperphosphorylation and neurodegeneration[J]. PLoS Genet, 2012, 8(11):e1003021.
24.	Pooler AM, Usardi A, Evans CJ, et al. Dynamic association of Tau with neuronal membranes is regulated by phosphorylation[J]. Neurobiol Aging, 2012, 33(2):431. e27-431.e38.

1. Hirai K, Aliev G, Nunomura A, et al. Mitochondrial abnormalities in Alzheimer's disease[J]. J Neurosci, 2001, 21(9):3017-3023.
2. Wang X, Su B, Fujioka H, et al. Dynamin-like protein 1 reduction underlies mitochondrial morphology and distribution abnormalities in fibroblasts from sporadic Alzheimer's disease patients[J]. Am J Pathol, 2008, 173(2):470-482.
3. Wei Y, Qu MH, Wang XS, et al. Binding to the minor groove of the double-strand, tau protein prevents DNA from damage by peroxidation[J]. PLoS ONE, 2008, 3(7):e2600.
4. Manczak M, Reddy PH. Abnormal interaction between the mitochondrial fission protein Drp1 and hyperphosphorylated Tau in Alzheimer's disease neurons:implications for mitochondrial dysfunction and neuronal damage[J]. Hum Mol Genet, 2012, 21(11):2538-2547.
5. Manczak M, Sesaki H, Kageyama Y, et al. Dynamin-related protein 1 heterozygote knockout mice do not have synaptic and mitochondrial deficiencies[J]. Biochim Biophys Acta, 2012, 1822(6):862-874.
6. Jellinger KA. Challenges in neuronal apoptosis[J]. Curr Alzheimer Res, 2006, 3(4):377-391.
7. DuBoff B, Gotz J, Feany MB. Tau promotes neurodegeneration via DRP1 mislocalization in vivo[J]. Neuron, 2012, 75, 618-632.
8. Schulz KL, Eckert A, Rhein V, et al. A new link to mitochondrial impairment in Tauopathies[J]. Mol Neurobiol, 2012, 46(1):205-216.
9. Kopeikina KJ, Carlson GA, Pitstick R, et al. Tau accumulation causes mitochondrial distribution deficits in neurons in a mouse model of Tauopathy and in human Alzheimer's disease brain[J]. Am J Pathol, 2011, 179(4):2071-2082.
10. Michal C, Dzhamilja S, Mailis L, et al. Principles of the mitochondrial fusion and fission cycle in neurons[J]. J Cell Sci, 2013, 126(10):2187-2197.
11. Dixit R, Ross JL, Goldman YE, et al. Differential regulation of dynein and kinesin motor proteins by Tau[J]. Science, 2008, 319(5866):1086-1089.
12. Stoothoff W, Jones PB, Spires-Jones TL. Differential effect of three-repeat and four-repeat Tau on mitochondrial axonal transport[J]. J Neurochem, 2009, 111(2):417-427.
13. McVicker DP, Chrin LR, Berger CL. The nucleotide-binding state of microtubules modulates kinesin processivity and the ability of Tau to inhibit kinesin-mediated transport[J]. J Biol Chem, 2011, 286(50):42873-42880.
14. Tatebayashi Y, Haque N, Tung YC, et al. Role of Tau phosphorylation by glycogen synthase kinase-3beta in the regulation of organelle transport[J]. J Cell Sci, 2004, 117(9):1653-1663.
15. Shahpasand K, Uemura I, Saito T, et al. Regulation of mitochondrial transport and inter-microtubule spacing by Tau phosphorylation at the sites hyperphosphorylated in Alzheimer's disease[J]. J Neurosci, 2012, 32(7):2430-2441.
16. Kanaan NM, Morfini G, Pigino G, et al. Phosphorylation in the amino terminus of Tau prevents inhibition of anterograde axonal transport[J]. Neurobiol Aging, 2012, 33(4):826.e15-826.e30.
17. Quintanilla RA, Matthews-Roberson TA, Dolan PJ, et al. Caspase-cleaved Tau expression induces mitochondrial dysfunction in immortalized cortical neurons:implications for the pathogenesis of Alzheimer disease[J]. J Biol Chem, 2009, 284(28):18754-18766.
18. Amadoro G, Corsetti V, Stringaro A,et al. A NH2 Tau fragment targets neuronal mitochondria at AD synapses:possible implications for neurodegeneration[J]. J Alzheimers Dis, 2010, 21(2):445-470.
19. Rhein V, Song X, Wiesner A, et al. Amyloid-beta and Tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer's disease mice[J]. Proc Natl Acad Sci USA, 2009, 106(47):20057-20062.
20. Atlante A, Amadoro G, Bobba A, et al. A peptide containing residues 26-44 of Tau protein impairs mitochondrial oxidative phosphorylation acting at the level of the adenine nucleotide translocator[J]. Biochim Biophys Acta, 2008, 1777(10):1289-1300.
21. Van der Jeugd A, Ahmed T, Burnouf S, et al. Hippocampal Tauopathy in Tau transgenic mice coincides with impaired hippocampus-dependent learning and memory, and attenuated late-phase long-term depression of synaptic transmission[J]. Neurobiol. Learn Mem, 2011, 95:296-304.
22. Manczak M, Hemachandra Reddy P. Abnormal interaction of VDAC1 with amyloid beta and phosphorylated Tau causes mitochondrial dysfunction in Alzheimer's disease[J]. Hum Mol Genet, 2012, 21(23):5131-5146.
23. Merkwirth C, Martinelli P, Korwitz A, et al. Loss of prohibitin membrane scaffolds impairs mitochondrial architecture and leads to Tau hyperphosphorylation and neurodegeneration[J]. PLoS Genet, 2012, 8(11):e1003021.
24. Pooler AM, Usardi A, Evans CJ, et al. Dynamic association of Tau with neuronal membranes is regulated by phosphorylation[J]. Neurobiol Aging, 2012, 33(2):431. e27-431.e38.

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West China Medical Journal

Tau蛋白对阿尔茨海默病线粒体形态分布及功能的影响机制的研究进展

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