4th International Conference on Neurology and Brain Disorders

September 09-11, 2021

September 09 -11, 2021 | Virtual Event
INBC 2017

Cristine Alves da Costa

Speaker at International Conference on Neurology and Brain Disorders 2017 - Cristine Alves da Costa
Institut de Pharmacologie Moléculaire et Cellulaire, France
Title : Parkin and p53 functional interplay in parkinson’s disease and brain tumors physiopathology

Abstract:

PD is a complex age-associated neurodegenerative disorder characterized by a progressive loss of midbrain dopamine neurons in the substantia nigra. Although, mainly of sporadic origin, the identification and characterization of PDassociated gene products, strongly contributed to the delineation of the major physiological processes disrupted in sporadic PD. Thus, in early 90s the search of gene candidates associated to either autosomal dominant or recessive familial PD-forms, led to the identification of Parkin (PRKN) mutations as key triggers of most juvenile autosomal recessive (ARJP) cases of PD. Thus, Parkin (Pk) has been shown to be an E3-ligase responsible for the physiological degradation by the proteasomal machinery of a considerable number of substrates. We recently established a new function of Pk as a transcription factor. We showed that Pk represses expression and activity of the pro-apoptotic tumor suppressor p53 independently of its E3-ligase function. Interestingly p53 is a key transcription factor involved in either neurodegenerative diseases due to its proapoptotic function or cancer due to its tumor suppressor properties. This led us to study the implication of parkin in glioma etiology. We have demonstrated that parkin expression is drastically reduced according to the grade in gliomas of distinct origins and that the reduction of parkin expression in human biopsies was associated to p53 inactivation by mutations. We show that endogenous and overexpressed p53 control parkin transcription ex-vivo and vivo. In conclusion, we delineated a functional interplay between parkin and p53 that allow their respective homeostasis in normal conditions suggesting that the dysfunction of this retro control may be at the origin of both Parkinson’s disease and gliomas.

Biography:

Dr. Cristine Alves da Costa is a neurobiologist and she received PhD Degree from the University of Sao Paulo USP, Brazil. She is a research director at INSERM and drives a team at the “Institute of Pharmacology Moleculaire et Cellulaire”. Her work has been recognized by various honors including the Scientific Prize of Excellence (PES) INSERM. Actually, she drives a team that works in the study of the implication of Parkinson’s disease associated proteins in the origin of cell death in neurodegenerative disorders and tumor suppression. Her research interests include Parkinson’s and Alzheimer’s disease molecular and cell biology, apoptosis and p53. Moreover, she is also interested in the interplay between these two pathologies via common molecular denominators and the link between neurodegenerative disorders and human brain cancer.

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