My research interest is to understand, using aged patient-derived induced neurons obtained from fibroblasts, how alterations in autophagy contribute to healthy ageing and the pathophysiology of age-related, chronic neurodegenerative disorders such as
Alzheimer’s Disease (AD), Huntington’s disease (HD) and Parkinson’s disease (PD).
Neurodegenerative disorders are a growing burden in our aging society. With longer life expectancy neurodegenerative disorders will become an even more serious public health issue influencing the active time of the elderly. Accumulating evidence are pointing at impairments in autophagy, a lysosomal degradation pathway, as playing a critical role in ageing and age-related neurodegenerative diseases. However, a clear mechanistic understanding of how alterations in autophagy causes cellular dysfunction and neuronal death, is currently lacking.
The overall aim of this project is to understand how alterations in autophagy contribute to the pathophysiology of chronic incurable neurodegenerative disorders of the central nervous system, such as Alzheimer’s Disease (AD), Huntington’s disease (HD) and Parkinson’s disease (PD). More specifically the aims of this study is to i) shed light on impairments of autophagy in neurodegenerative diseases of the CNS, ii) screen for drugs restoring these defects and iii) validate the best candidates. This will be achieved by using models that we have recently developed specifically to study autophagy impairments in neurodegenerative diseases. The model is based on direct neuronal reprogramming of patient derived fibroblasts. This approach will allow to tackle the vulnerability of neurons to different protein build up in a system that is not only of human origin, but also patient specific with carrying the aging signature of the donor.This information will be instrumental to develop novel treatment strategies for proteinopathies, including Parkinson’s, Huntington’s and Alzheimer’s disease, given their shared alteration in autophagy.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 739593. HCEMM supported by EU Programme: H2020-EU.4.a. – Teaming of excellent research institutions and low performing RDI regions. Project starting date was 1 April 2017.
Hungarian Centre of Excellence for Molecular Medicine is a strong catalyst of reformative changes in biomedical science and in institutional research management.
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