Telomerase Improves PD Symptoms and Pathology

A telomerase protein called TERT has been shown to protect neurons and the brain.

TERT protein has been demonstrated to accumulate in the mitochondria of Alzheimer’s disease (AD) brains and to protect primary mouse neurons from pathogenic tau in the past. In order to enhance telomerase expression in a mouse model of Parkinson’s disease (PD) overexpressing human wild type -synuclein, we used telomerase activators. Our goal was to see if higher Tert expression levels could help with PD symptoms and stimulate protein degradation.
Despite the fact that telomere length in the examined region remained identical, increased Tert expression in the brain for both activators was linked to significant improvements in motor skills such as gait and motor coordination. Only one activator (TA-65) resulted in a reduction in reactive oxygen species in brain mitochondria. Importantly, we show that total, phosphorylated, and aggregated -synuclein levels in the hippocampus and neocortex of activator-treated mice were much lower, corresponding to increased autophagy markers, implying greater breakdown of hazardous alpha-synuclein. We infer that telomerase activators produce higher Tert expression, which is linked to lower levels of -synuclein protein, either by activating autophagy or by inhibiting or delaying degradation pathways that are compromised during disease progression. This excellent preclinical research could pave the way for novel treatment options for neurodegenerative illnesses like Parkinson’s.

Author (S) Details

Tengfei Wan
Biosciences Institute, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK.

Emma J. Weir
Biosciences Institute, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK.

Mary Johnson
Translational and Clinical Research Institute, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK.

Viktor I. Korolchuk
Biosciences Institute, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK.

Gabriele C. Saretzki
Biosciences Institute, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK.

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