Progressive supranuclear palsy: what do we know about it?

Progressive supranuclear palsy (PSP) is a progressive tauopathy characterized by supranuclear ophthalmoplegia, pseudobulbar palsy, dysarthria, axial rigidity, frontal lobe dysfunction, and dementia. The typical pathology includes neuronal loss, gliosis and microtubule-associated protein tau (MAPT)-positive inclusions in neurons and glial cells, primarily in basal ganglia, brainstem and cerebellum. The pathogenesis of PSP is not yet completely understood; however, there are several hypotheses. This article reviews the present knowledge about PSP, and the concepts underlying mitochondrial dysfunction, lipoperoxidation, and gene mutations. The clinical features of PSP are also discussed; these include vertical gaze palsy, pseudobulbar palsy, aphasia, dysarthria, axial rigidity, and neuropsychiatric symptoms, such as amnesia, irritability, loss of interest, and dementia. In terms of diagnosis, there is considerable interest in neuroimaging for detecting PSP; therefore, neuroimaging techniques such as magnetic resonance imaging (MRI) and [18F]- fluorodeoxyglucose positron-emission tomography (FDG-PET) are reviewed. A definitive diagnosis of PSP depends on pathology, and the introduction of new clinical subtypes challenges presents the widely adopted diagnosis criteria. PSP treatments such as serotonin antagonists, α2 receptor antagonists, and coenzyme Q10 are also discussed. There is no curative therapy for PSP; all of the available treatments are palliative.

Simvastatin induces neuroprotection in 6-OHDA-lesioned PC12 via the PI3K/AKT/caspase 3 pathway and anti-inflammatory responses.

BACKGROUND: In addition to their original applications for lowering cholesterol, statins display multiple neuroprotective effects. Inflammatory reactions and the PI3K/AKT/caspase 3 pathway are strongly implicated in dopaminergic neuronal death in Parkinson's disease (PD). This study aims to investigate how simvastatin affects 6-hydroxydopamine-lesioned PC12 via regulating PI3K/AKT/caspase 3 and modulating inflammatory mediators. METHODS: 6-hydroxydopamine-treated PC12 cells were used to investigate the neuroprotection of simvastatin, its association with the PI3K/AKT/caspase 3 pathway, and antiinflammatory responses. Dopamine transporters (DAT) and tyrosine hydroxylase (TH) were examined in 6-hydroxydopamine-treated PC12 after simvastatin treatment. RESULTS: Simvastatin-mediated neuroprotection was associated with a robust reduction in the upregulation induced by 6-OHDA of inflammatory mediators including IL-6, COX2, and TNF-α. The downregulated DAT and TH levels in 6-OHDA-lesioned PC12 were restored after simvastatin treatment. Simvastatin reversed 6-OHDA-induced downregulation of PI3K/Akt phosphorylation and attenuated 6-OHDA-induced upregulation of caspase 3 in PC12. Furthermore, the PI3K inhibitor LY294002 pronouncedly abolished the simvastatin-mediated attenuation in caspase 3. CONCLUSIONS: Our results demonstrate that simvastatin provides robust neuroprotection against dopaminergic neurodegeneration, partially via antiinflammatory mechanisms and the PI3K/Akt/caspase 3 pathway. These findings contribute to a better understanding of the critical roles of simvastatin in treating PD and might elucidate the molecular mechanisms of simvastatin effects in PD.