Jose Vicente Sanchez Mut (Spain)
Instituto de Neurociencias de Alicante
Molecular Neurobiology and Neuropathology
Jose V. Sanchez-Mut is a principal investigator at the Neuroscience Institute of Alicante, Spain. He received a B.S. in Biology from the University of Valencia (2005, Spain) and a PhD in Neurosciences from the Autonomous University of Barcelona (2014, Spain). He conducted his PhD training at the laboratory of Cancer Epigenetics lead by Prof. Manel Esteller at the Bellvitge Biomedical Research Institute (IDIBELL, Barcelona) and his postdoctoral training at the laboratory of Neuro-epigenetics headed by Prof. Gräff at the École Polytechnique Fédérale de Lausanne (EPFL, 2014-2020, Switzerland). From May 1st 2020, he is leading the laboratory of Functional Epi-Genomics of Aging and Alzheimer's Disease at the Neuroscience Institute of Alicante. His studies investigate the epigenetic underpinnings of brain function in physiological and pathological conditions. He has contributed to the recognition of the epigenetic specificity of different brain regions and cell types, highlighted circadian epigenetic alterations in neurodevelopmental syndromes, and identified genetic and epigenetic alterations in neurodegenerative diseases. His most recent studies investigate the contribution of the genetic-epigenetic interactions to the development of aging and Alzheimer’s disease alterations.

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PM20D1-DERIVED TREATMENT DECREASES AMYLOID PATHOLOGY AND IMPROVES COGNITIVE PERFORMANCE IN C.ELEGANS AND MOUSE MODELS OF ALZHEIMER´S DISEASE

Session Name
0400 - AD ANIMAL MODELS & TRANSLATIONAL ASPECTS (ID 97)
Session Type
SYMPOSIUM
Date
Wed, 16.03.2022
Session Time
04:15 PM - 06:00 PM
Room
ONSITE: 131-132
Lecture Time
05:00 PM - 05:15 PM
Presenter

Abstract

Aims

Alzheimer’s disease (AD) is a complex disorder caused by a combination of genetic and non-genetic factors, which are investigated by genome- (GWAS) and epigenome- (EWAS) wide association studies, respectively. Combining the strengths of both type of studies, we have recently identified a new genetic-epigenetic interaction on Peptidase M20 Domain Containing 1 (PM20D1) associated with AD. We showed that PM20D1 expression depends on a haplotype-dependent chromatin loop between PM20D1 enhancer and promoter regions, that PM20D1 expression is increased by AD-like stressors, and that its overexpression improves cognitive performance and reduces AD pathologies. However, the precise mechanism by which PM20D1 exerts its protective role in AD remains largely unknown. PM20D1 facilitates the condensation of fatty acids and amino acids generating a series of compounds named N-acyl amino acids (NAAs). NAAs are present in all tissues, including brain, yet little is known about their function and regulation.

Methods

To investigate their role in AD, we NAA-treated AD primary cultures, worms and mouse models, and measured AD-related pathologies and cognitive performance. Furthermore, to unveil the underlying mechanisms, we applied snRNA-seq approaches and cell-type specific manipulations.

Results

Following this approach, we demonstrate that NAAs modify the cellular phase of AD and improves cell survival, amyloid burden and cognitive performance.

Conclusions

Our results therefore support the use of NAAs as a therapeutic approach for AD.

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