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Neurosci Lett. 2014 May 21;569:131-6. doi: 10.1016/j.neulet.2014.03.075. Epub 2014 Apr 8.

TDP-43 interaction with the intracellular domain of amyloid precursor protein induces p53-associated apoptosis.

Author information

1
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, the Second Affiliated Hospital, Soochow University, Suzhou, China.
2
Affiliated Bayi Brain Hospital, Beijing Military General Hospital, Beijing, China.
3
Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
4
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, the Second Affiliated Hospital, Soochow University, Suzhou, China. Electronic address: h999.judy@gmail.com.

Abstract

TAR DNA-binding protein 43 (TDP-43), an essential pathological protein in both amyotrophic later sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), is expressed abnormally in Alzheimer's disease (AD). However, whether and how TDP-43 contributes the pathogenesis of AD remains unknown. We have shown here a colocalization between TDP-43 and the intracellular domain of APP (AICD) in the nucleus. Coimmunoprecipitation analysis showed an interaction between TDP-43 and AICD. Overexpression of TDP-43 in COS7 cells enhanced the transactivation of AICD in an APP-Gal4 luciferase reporter system. Real-time PCR analysis showed that cotransfection of TDP-43 and AICD in HEK293 cells increased P53 mRNA levels compared to either TDP-43-transfected or AICD-transfected cells. Moreover, cotransfection of TDP-43 and AICD in either N2a or COS7 cells showed increased numbers of apoptotic cells compared to either TDP-43-transfected or AICD-transfected cells, indicating that TDP-43 enhances AICD-mediated apoptosis in N2a or COS7 cells. Thus, TDP-43 may play a role in AD pathology through interaction with AICD.

KEYWORDS:

Alzheimer's disease; Amyloid precursor protein; TAR DNA-binding protein 43; The intracellular domain of APP

PMID:
24721672
DOI:
10.1016/j.neulet.2014.03.075
[Indexed for MEDLINE]

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