Laboratory for Alzheimer's Disease
Laboratory Head
Akihiko TAKASHIMA (Ph.D.)
Alzheimer's disease(AD) is one of the most devastating brain diseases in middle aged and elderly humans in the modern society. This disease is characterized clinically by progressive loss of memory and other cognitive functions, resulting in severe dementia. To develop a therapeutic strategy for Alzheimer's disease, it is very important to understand the basic molecular mechanisms of the disease. Alzheimer's disease is histochemically characterized by loss of neurons, the accumulation of amyloid β(beta) protein (Aβ) in senile plaques, and the accumulation of abnormally phosphorylated tau in neurofibrillary tangles (NFT), neuropil threads and plaque associated neurites. The loss of neurons is proportional to the degree of dementia. The mechanism of tau phosphorylation may afford some insights into the cellular events in the AD brain. In this laboratory, we are focusing on the loss of neurons in the AD brain, approaching the problem from the mechanism of Aβ neurotoxicity and tau phosphorylation perspectives.
- Role of Presenilin in Alzheimer's disease
- Molecular mechanisms of neurofibrillary tangles and neuronal death
- Generation and analysis of model animals for neurodegeneration
- April 03, 2009
- Memory maintenance
Inhibiting GSK-3β, a molecule that causes Alzheimer disease pathology, may also create memory problems
- Stotiopoulos I, Cerqueira JJ, Catania C, Takashima A, Sousa N, Almeida OFX.
"Stress and glucocorticoid footprints in the brain-the path from depression to Alzheimer's disease."
Neuroscience & Behavioral Reviews (in press) - Planel E, Tatebayashi Y, Miyasaka T, Liu L, Wang L, Herman M, Yu WH, Luchsinger JA, Wadzinski B, Duff KE, Takashima1 A.
"Insulin dysfunction induces in vivo tau hyperphosphorylation through distinct mechanisms."
J. Neurosci 27(50):13635-48 (2007) - Takashima A
"Study of Al on AD pathology-in vitro vs in vivo evidence"
J. Alzheimers Disease (in press) - Yoshiike Y, Kayed R, Milton SC, Takashima A, Glabe CG.
"Pore-forming proteins share structural and functional homology with amyloid oligomers."
Neuromolecular Med. 9(3) 270-5 (2007) - Takashima A.
"Neuronal deregulation of tau phosphorylation: Implications for mechanism and treatment of Alzheimer's Disease."
Research Progress in Alzheimer's Disease and Dementia Nova Science Publishers, Inc. 61-78 (2007) - Yoshiike Y, Akagi T, & Takashima A
"Surface structure of amyloid-beta fibrils contributes to cytotoxicity"
Biochemistry. 46(34), 9805-12 (2007) - Kimura T, Yamashita S, Fukuda T, Park J-M, Murayama M, Mizoroki T, Yoshiike Y, Sahara N, and Takashima A
"Hyperphosphorylated tau in parahippocampal cortex impairs place learning in aged mice expressing wild-type human tau"
The EMBO Journal. 26(24), 5143-5152 (2007) - Maeda S, Sahara N, Kim H, Saito Y, Akagi T, Miyasaka T, Hashikawa T, Murayama S, Ikai A, Takashima A
"Granular tau oligomers as intermediates of tau filaments."
Biochem. 46(12):3856-61 (2007) - Shimojo M, Sahara N, Murayama M, Ichinose H, Takashima A
"Decrease Aβs secretion in Familial Alzheimer's disease-linked mutant Presenilin 1."
Neurosci. Res. 57(3):446-53(2007) - Ueno H, Murayama O, Maeda S, Sahara N, Park JM, Murayama M, Sanda A, Iwahashi K, Matsuda M, Takashima A
"Novel conformation-sensitive antibodies specific to three- and four-repeat tau"
Biochem. Biophys. Res. Commun. 358(2) 602-607(2007)