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Rational therapeutic approaches to progressive supranuclear palsy Stamelou M; de Silva R; Arias-Carrion O; Boura E; Hollerhage M; Oertel WH; Muller U; Hoglinger GUBrain 2010[Jun]; 133 (Pt 6): 1578-90Progressive supranuclear palsy is a sporadic and progressive neurodegenerative disease, most often presenting as a symmetric, akinetic-rigid syndrome with postural instability, vertical supranuclear gaze palsy and frontal lobe deficits. It belongs to the family of tauopathies and involves both cortical and subcortical structures. Although the exact pathophysiology is not yet fully understood, several lines of evidence point to a crucial contribution from both genetic predisposition and mitochondrial dysfunction. Recently gained insights into the pathophysiology of this disease have led to several hypothesis-driven therapeutic approaches aiming at disease-modification rather than mere symptomatic neurotransmitter-replacement therapy. Agents targeting mitochondrial dysfunction have already shown a positive effect in a phase II study and further studies to verify and expand these results are ongoing. Clinical studies with agents targeting tau dysfunction such as tau-kinase inhibitors, tau-aggregation inhibitors and microtubule stabilizers are in preparation or ongoing. This review presents the current pathophysiological concepts driving these exciting therapeutic developments.|Animals[MESH]|Humans[MESH]|Mitochondria/physiology[MESH]|Supranuclear Palsy, Progressive/*drug therapy/genetics/*physiopathology[MESH] |
