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P1–426: Different neurobiological bases of episodic and semantic confabulations in Alzheimer's disease: The Osaki–Tajiri project (4)
Author(s) -
Lee Eunjoo,
Meguro Kenichi,
Kinomura Shigeo,
Akanuma Kyoko,
Yamaguchi Satoshi,
Ishii Hiroshi,
Sugamata Kenji,
Yoshioka Seiro,
Mori Etsuro
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.805
Subject(s) - delusion , confabulation (neural networks) , psychology , orbitofrontal cortex , neuropsychology , audiology , episodic memory , semantic memory , cognitive psychology , neuroscience , cognition , psychiatry , medicine , prefrontal cortex
several other human ROCO proteins have been implicated in cancer and cell-death. Objective: To study the molecular function of human LRRK2. Method: Human LRRK2 cDNA was cloned into mammalian expression vectors. The generated expression constructs were transfected into M17 human neuroblastoma and 293 kidney cell lines. In vitro kinase assay was performed to measure phosporylation of myelin basic protein in the presence of [P] ATP. Result: In vitro kinase assay using full length recombinant LRRK2 showed increased phosphorylation activities upon GTP binding in a dose-dependent manner. We show that LRRK2 is a novel protein kinase whose activity is self-regulated by its internal GTPase. Conclusion: Our finding suggests that LRRK2 is a unique MAPKKK activated by its intramolecular GTPase. Since both GTPase and MAPKKK are regulators of signal transduction cascades, LRRK2 is likely to play an important role in cell function and survival in response to biological and injurious stimuli. It has been reported that phosphorylation of PD-related proteins such as alpha-synuclein and parkin results in a change in protein solubility and enzymatic activity, respectively. It will be of great interest to investigate whether LRRK2 regulates the phosphorylation and function of these PD-related proteins. We propose a model in which mutations in LRRK2 may trigger an aberrant signal transduction cascade that ultimately leads to neurodegeneration and development of PD.