Speech Title: Increased telomerase improves motor function and alpha-synuclein pathology in a transgenic mouse model of Parkinson's disease associated with enhanced autophagy

About the speaker:

Dr. Gabriele Saretzki’s research interests are devoted to the role of telomerase in ageing and cancer and under oxidative stress. She focuses particularly on non-telomeric and non-canonical roles of telomerase. They and others have found that telomerase shuttles from the nucleus to mitochondria under oxidative stress. Her group was the first to describe a protective role of telomerase and its protein part TERT onto mitochondria (Ahmed et al., 2008). They recently found that cancer cells protect themselfs from external stress by mitochondrial localisation of telomerase which decreases nuclear damage and apoptosis and is therefore a pro-survival mechanism (Singhapol et al., 2013). Since adult neurons do not express telomerase activity but still express TERT, the protein part of telomerase, they demonstrated recently that this could protect neurons from oxidative damage and neurodegenerative agents such as hyperphosphorylated tau (Spilsbury et al., 2015). They also used embryonic mouse neurons from telomerase/TERT deficient as well as wild type mice and transduced them with lentiviruses against a mutant (P301L) tau protein and showed more oxidative stress and lipid peroxidation in neurons lacking TERT compared to wild type neurons (Spilsbury et al., 2015). Thus TERT seems to protects neurons against hyperphosphorylated tau protein which induces neurodegeneration in the context of Alzheimer's disease and other tauopaties. They propose that boosting TERT levels in the brain using known telomerase activators could help prevent or ameliorate neurodegenerative diseases and dementia related to it. She has introduced new methods for measuring cognitive properties such as Barnes maze (learning and memory) and locomotor tests for mice in her institute.

Prof. Thierry Léveillard

Research Director

Clinical Professor

INSERM

Department of Genetics, Institut de la Vision

France

Speech Title: Metabolic signaling impairment in the progression of Alzheimer's disease

About the speaker:

Prof. Thierry Léveillard obtained his PhD at the University of Rouen (France) in 1989, following a Masters in Biochemistry at the University Pierre and Marie Curie in Paris. His current project was initiated in Strasbourg where he was recruited as “Chargé de rechercheInserm” in 1998 and ultimately continued in Paris where he was promoted “Directeur de recherche” in 2006. The diverse influences of these different geographic locations translate to a broad expertise in molecular biology. He commenced his current medical project on signaling and the therapy of inherited retinal degeneration with José Sahel. One novel scientific achievement, the yields of which have occupied most of his time over the last ten years, was based on the observations made by Saddek Mohand-Saïd and José Sahel in a mouse model of retinitis pigmentosa (RP). The transplantation of rod photoreceptors in the eye of this mouse was found to prevent the secondary loss of cones, the more vital class of photoreceptors necessary for vision. In the degenerative disease RP, most patients carry a mutation in a gene (among many) expressed selectively in rods, hence preventing secondary cone loss by means of mimicking the effects of transplantation could be an effective and broadly applicable therapy. Two studies published respectively in PNAS and IOVS demonstrated that the molecules are proteins secreted by rods, but did not allow for their isolation. He designed a protocol of systematic screening of a retinal library against primary cone cultures from chicken embryos. This strategy of expression cloning was inspired by the emerging concepts from the field of functional genomics. The identification of this novel member of the thioredoxin family, which published in 2004 in Nature Genetics, resulted in their being honoured alongside José Sahel with the 2005 American foundation FFB award.

Dr. Jiali Li (Session Chair)

Professor and Principal Investigator

Peking University Health Science Center

IDG/McGovern Institute for Brain Research

China

About the Session Chair:

Dr. Jiali Li obtained his PhD in Shanghai Medical School at the Fudan University in 2003. Research interests in Li's laboratory are mainly focused on deciphering molecular and epigenetic bases in brain aging and age-related neurodegenerative diseases. Using animal models from rodent to nonhuman primate, his laboratory has investigated that the regulatory roles of distinct epigenetic systems including histone modification, DNA methylation and demethylation, and non-coding RNAs in brain aging and neurodegenerative diseases. Among the laboratory's accomplishments and ongoing activities are: (i) Regulatory role of long noncoding RNAs (lncRNAs) and circular RNAs (ciRNAs) in brain aging and age-related neurodegenerative diseases (Liu et al., Genome Res, 2017; Xu et al., Cell Discovery, 2018; and Xu et al., Nat Commun.2020); (ii) Contribution of abnormal histone acetylation and DNA demethylation to the pathogenesis of neurodegenerative diseases (Li et al., Nat Med, 2012; Li et al., Nat Neurosci., 2013; Jiang et al., Brain, 2015; Jiang et al., EMBO Rep., 2017;. FASEB J, 2020).