Abstract
One of the tuberous sclerosis complex (TSC) gene products, tuberin is assumed to be the functional component, being involved in a wide variety of cellular processes. Here, we report for the first time that tuberin dysfunction may represent a mechanism for neuronal damage in Alzheimer’s disease (AD), Parkinson’s disease with dementia (PD/DLB), and a mouse model of PD. Tuberin was hyperphosphorylated at Thr1462 in post-mortem frontal cortex tissue of both AD and PD/DLB patients and in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP). Both PTEN and Akt phosphoactivation corresponded to the hyperphosphorylation patterns of tuberin suggesting that the PTEN–Akt pathway might be the mechanism of tuberin phosphorylation. Our data provide new information regarding the possible role of tuberin dysfunction in major neurodegenerative disorders, such as AD and PD, whereby inhibition of tuberin function may trigger an onset of neuronal cell death.
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References
Kwiatkowski DJ (2002) Tuberous sclerosis: from tubers to mTOR. Ann Hum Genet 67:87–96
Mizugichi M, Hino O (2003) Neuropathology. In: Curatolo P (ed) Tuberous sclerosis complex: from basic science to clinical phenotypes, Mac Keith Press, London
Soucek T, Holzl G, Bernaschek G, Hengstschläger M (1998) A role of the tuberous sclerosis gene-2 product during neuronal differentiation. Oncogene 16:2197–2204
Ferrando-Miguel R, Rosner M, Freilinger A, Lubec G, Hengstschläger M (2005) Tuberin—A new molecular target in Alzheimer’s disease? Neurochem Res 30:1413–1419
Pan D, Dong J, Zhang Y, Gao X (2004) Tuberous sclerosis complex: from Drosophila to human disease. Trends Cell Biol 14:78–85
Xiao G-H, Shoarinejad F, Jin F, Golemis EA, Yeung RS (1997) The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis. J Biol Chem 272:6097–6100
Henry KW, Yuan X, Koszewski NJ, Onda H, Kwiatkowski DJ, Noonan DJ (1998) Tuberous sclerosis gene 2 product modulates transcription mediated by steroid hormone receptor family members. J Biol Chem 273:20535–20539
Soucek T, Pusch O, Wienecke R, DeClue JE, Hengstschläger M (1997) Role of the tuberous sclerosis gene-2 product in cell cycle control. J Biol Chem 272:29301–29308
Corradetti YMN, Inoki K, Guan K-L (2003) TSC2: filling the GAP in the mTOR signalling pathway. Trends Biochem Sci 29:32–38
Inoki K, Corradetti MN, Guan K-L (2004) Dysegulation of the TSC–mTOR pathway in human disease. Nat Genet 37:19–24
Acknowledgments
This work was supported in part by NIH grants NS38377 and NS48206 and grants from American Diabetes Association (ADA), U.S. Dept of Veterans Affairs (VA), American Parkinson’s Disease Association (APDA), Parkinson’s Disease Foundation (PDF), San Antonio Area Foundation (SAAF), and Executive Research Council (ERC) of UTHSCSA. T.M.D. is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases.
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Habib, S.L., Michel, D., Masliah, E. et al. Role of Tuberin in Neuronal Degeneration. Neurochem Res 33, 1113–1116 (2008). https://doi.org/10.1007/s11064-007-9558-8
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DOI: https://doi.org/10.1007/s11064-007-9558-8