Role of tuberin in neuronal degeneration.
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.
Habib
Samy L
SL
Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA.
Michel
David
D
Masliah
Eliezer
E
Thomas
Bobby
B
Ko
Han Seok
HS
Dawson
Ted M
TM
Abboud
Hanna
H
Clark
Robert A
RA
Imam
Syed Z
SZ
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D014402:Tuberous Sclerosis / Q000235:genetics / Q000473:pathology; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D013912:Threonine; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase