Frontrunner in Translation: Progressive Supranuclear Palsy.

Ali Shoeibi,Nahid Olfati,Irene Litvan

doi:10.3389/fneur.2019.01125

Abstract

Progressive supranuclear palsy (PSP) is a four-repeat tau proteinopathy. Abnormal tau deposition is not unique for PSP and is the basic pathologic finding in some other neurodegenerative disorders such as Alzheimer's disease (AD), age-related tauopathy, frontotemporal degeneration, corticobasal degeneration, and chronic traumatic encephalopathy. While AD research has mostly been focused on amyloid beta pathology until recently, PSP as a prototype of a primary tauopathy with high clinical-pathologic correlation and a rapid course is a crucial candidate for tau therapeutic research. Several novel approaches to slow disease progression are being developed. It is expected that the benefits of translational research in this disease will extend beyond the PSP population. This article reviews advances in the diagnosis, epidemiology, pathology, hypothesized etiopathogenesis, and biomarkers and disease-modifying therapeutic approaches of PSP that is leading it to become a frontrunner in translation.

Highlights

Progressive supranuclear palsy (PSP) is a primary tauopathy that is playing an increasingly important role in the field
This article reviews the advances in the diagnosis, epidemiology, pathology, hypothesized etiopathogenesis, and biomarkers and disease-modifying therapeutic approaches of PSP that is leading it to become a frontrunner in translation
Firearm use was significantly higher in incident PSP cases vs. controls; Higher, but not significant, history of Traumatic brain injury (TBI) in incident PSP cases vs. controls

Summary

INTRODUCTION

Progressive supranuclear palsy (PSP) is a primary tauopathy that is playing an increasingly important role in the field. PSP-Parkinsonism (PSP-P) is a retrospective diagnosis made after patients presenting with usually asymmetric parkinsonism with or without resting tremor or levodopa response resembling PD later develop typical PSP-RS features including postural instability and/or vertical supranuclear gaze palsy [34, 39]. Pathological criteria of PSP, were developed about 30 years later [75] and subsequently revised and validated in 1996 [76] providing the basis for PSP research till present It defines definite PSP as high density of NFTs and neuropil threads in at least three of these following areas: pallidum, subthalamic nucleus, substantia nigra, or pons. In its monomeric water-soluble state, tau takes a paperclip conformation [99] that keeps the phosphatase-activation domain

Findings

CONCLUSION

DISCLOSURE