Toggle Main Menu Toggle Search

Open Access padlockePrints

Cholinergic systems in progressive supranuclear palsy

Lookup NU author(s): Dr Naomi Warren, Dr Margaret Piggott, Emeritus Professor Elaine Perry, Professor David Burn

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disease characterized by akinetic-rigid features, falls, a supranuclear gaze palsy and subcortical dementia. Pathologically, there is abnormal accumulation of tau protein. Cholinergic deficits are thought to underlie the postural instability and cognitive impairment of PSP, but trials of cholinergic agonists and cholinesterase inhibitors have failed to show improvement in motor function, quality of life and cognitive impairment. The five cortico-basal ganglia loops, linking functionally related areas of the brain, are damaged in PSP, leading to specific clinical deficits. Cholinergic dysfunction is related to loss of cholinergic interneurons in the striatum, compounded by reduced inputs into the circuits from other cholinergic nuclei, such as the pedunculopontine nucleus and nucleus basalis of Meynert. Normal cholinergic transmission requires the presence of intact cholinergic neurons capable of releasing sufficient acetylcholine, and functional muscarinic and nicotinic receptors. Whilst there is evidence from autopsy and in vivo studies of loss of cholinergic neurons in PSP, the receptor status is unknown. This may be critical to understanding the basis for the poor therapeutic response to cholinomimetics. Symptomatic treatment using cholinergic drugs may thus be improved by more specific targeting of cholinergic receptors or nuclei. There is also evidence that cholinergic agents may have disease-modifying effects. This article reviews the key clinical features of PSP, along with normal basal ganglia anatomy and cholinergic transmission. Cholinergic deficits based on clinical and neurochemical parameters are then discussed, before concluding with suggested future directions for cholinergic treatments.


Publication metadata

Author(s): Warren NM, Piggott MA, Perry EK, Burn DJ

Publication type: Review

Publication status: Published

Journal: Brain

Year: 2005

Volume: 128

Issue: 2

Pages: 239-249

Print publication date: 01/02/2005

ISSN (print): 0006-8950

ISSN (electronic): 1460-2156

URL: http://dx.doi.org/10.1093/brain/awh391

DOI: 10.1093/brain/awh391

PubMed id: 15649952


Actions

Find at Newcastle University icon    Link to this publication


Share