Validation of Hes3 and TPM4 as novel biomarkers in neurology and neuro-oncology for clinical practice *WITH VIDEO*

Despite great progress in medicine, two categories of serious disorders affecting the brain are in dire need of novel therapeutic approaches: Neurological disorders (including various neurodegenerative diseases and stroke) and brain cancer (including gliomas). These two groups of afflictions are often studied separately, in different academic departments. However, they both involve the endogenous regeneration mechanisms of the central nervous system. In neurological disorder, identifying and activating endogenous tissue repair mechanisms will lead to new therapeutic concepts. The two applicants, in a past collaborative effort, discovered such a mechanism (the “Hes3 Signaling Axis) in endogenous neural stem cells; by activating it using soluble factors, they induced motor function improvements in preclinical rodent models of ischemic stroke. Subsequent work demonstrated that activation of the Hes3 Signaling Axis also induced functional improvements in Parkinsonian models. Conversely, genetic suppression resulted in enhanced tissue damage and deficient regeneration in models of demyelination and diabetes (i.e., the function of the pathway is not confined to brain tissue).