Telomerase Improves PD Symptoms and Pathology

TERT, a telomerase protein, has been demonstrated to protect neurons and the brain.

TERT protein has previously been shown to accumulate in the mitochondria of Alzheimer's disease (AD) brains and protect primary mouse neurons from pathogenic tau. This prompted us to employ telomerase activators in order to boost telomerase expression in a mouse model of Parkinson’s disease (PD) overexpressing human wild type
-synuclein. Our aim was to test whether increased Tert expression levels were able to ameliorate PD symptoms and to activate protein degradation.

Increased Tert expression in the brain for both activators was shown to be associated with significant improvements in motor functions such as gait and motor coordination, despite the fact that telomere length in the studied region remained unchanged. Interestingly, only one activator (TA-65) resulted in a decrease of reactive oxygen species from brain mitochondria. Importantly, we demonstrate that total, phosphorylated and aggregated
-synuclein were significantly decreased in the hippocampus and neocortex of activator-treated mice corresponding to enhanced markers of autophagy suggesting an improved degradation of toxic alpha-synuclein. We conclude that increased Tert expression caused by telomerase activators is associated with decreased
-synuclein protein levels either by activating autophagy or by preventing or delaying degradation mechanisms which are impaired during disease progression. This promising preclinical data could lead to new therapy options for neurodegenerative diseases like Parkinson's disease.