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Parkinson’s Disease: Basic Pathomechanisms and a Clinical Overview

Chapter
First Online:
Part of the Advances in Neurobiology book series (NEUROBIOL, volume 15)

Abstract

PD is a common and a debilitating degenerative movement disorder. The number of patients is increasing worldwide and as yet there is no cure for the disease. The majority of existing treatments target motor symptom control. Over the last two decades the impact of the genetic contribution to PD has been appreciated. Significant discoveries have been made, which have advanced our understanding of the pathophysiological and molecular basis of PD. In this chapter we outline current knowledge of the clinical aspects of PD and the basic mechanistic understanding.

Keywords

Parkinson’s disease Genetic risk Environmental factors Clinical features Treatment Pathology Lewy body Prion-like mechanisms Neuroinflammation Autophagy/lysosomal dysfunction 

Abbreviations

8-OHDG

8-Hydroxy-2-deoxyguanosine

APOE

Apolipoprotein E

ATP13a2

ATPase 13a2

COMT

Catechol-O-methyl transferase

CT

Computed tomography

DAergic

Dopaminergic

DAT

Dopamine transporter

DaTSCAN

Dopamine transporter scan

DaTSPECT

Dopamine transporter single photon emission computed tomography

DLB

Dementia with Lewy bodies

DMV

Dorsal motor nuclear complex of cranial nerves IX and X

EDS

Excessive daytime sleepiness

GABA

Gamma-aminobutyric acid

GBA

Glucocerebrosidase beta acid

GD

Gaucher’s disease

HNE

4hydroxy2-nonenal

IL1

Interleukin1

iNOS

Inducible nitric oxide synthase

iPS

Induced pluripotent stem cell

LBs

Lewy bodies

LN

Lewy neurite

LRRK2

Leucine-rich-repeat kinase 2

MAO

Monoamine oxidase

MAOI

Monoamine oxidase inhibitor

MAPT

Microtubule-associated protein tau

MCI

Mild cognitive impairment

MIBG

123-meta iodobenzylguanidine radioactive tracer

MR

Magnetic resonance

MSA

Multiple system atrophy

NAC

Non-amyloid component

ND

Nigral degeneration

NFTs

Neurofibrillary tangles

PD

Parkinson’s disease

PDD

PD dementia

PET

Positron emission tomography

PSP

Progressive supranuclear palsy

QSBB

Queen Square Brain Bank

RBD

REM sleep behaviour disorder

REM

Rapid eye movement

RIPK

Receptor interacting protein kinase

ROS

Reactive oxygen species

SN

Substantia nigra

SNCA

Alpha-synuclein

SWEDD

Scans without evidence of dopamine deficit

TNF

Tumour necrosis factor

TREM2

Triggering receptor expressed on myeloid cells

UCHL1

Ubiquitin C-terminal hydrolase L1

UPDRS

Unified Parkinson’s disease rating scale

UPS

Ubiquitin proteasome system

VPS35

Vaboular protein sorting-associated protein 35

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Notes

Acknowledgements

AN is funded by a Career Development Award from Parkinson’s UK; RB is funded by the Reta Lila Weston Institute of Neurological Studies. This work was supported in part by the Wellcome Trust/MRC joint call in Neurodegeneration award (WT089698) to the UK Parkinson’s disease Consortium (UKPDC) whose members are from the UCL Institute of Neurology, University of Sheffield and the MRC protein phosphorylation unit Dundee.

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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Molecular Neuroscience, Reta Lila Weston Institute of Neurological StudiesUCL Institute of NeurologyLondonUK

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