PT  - JOURNAL ARTICLE
AU  - Pei-Lan Zhang
AU  - Yan Chen
AU  - Chen-Hao Zhang
AU  - Yu-Xin Wang
AU  - Pedro Fernandez-Funez
TI  - Genetics of Parkinson’s disease and related disorders
AID  - 10.1136/jmedgenet-2017-105047
DP  - 2017 Nov 18
TA  - Journal of Medical Genetics
PG  - jmedgenet-2017-105047
4099  - http://jmg.bmj.com/content/early/2017/11/18/jmedgenet-2017-105047.short
4100  - http://jmg.bmj.com/content/early/2017/11/18/jmedgenet-2017-105047.full
AB  - Parkinson’s disease (PD) is a complex and heterogeneous neurological condition characterised mainly by bradykinesia, resting tremor, rigidity and postural instability, symptoms that together comprise the parkinsonian syndrome. Non-motor symptoms preceding and following clinical onset are also helpful diagnostic markers revealing a widespread and progressive pathology. Many other neurological conditions also include parkinsonism as primary or secondary symptom, confounding their diagnosis and treatment. Although overall disease course and end-stage pathological examination single out these conditions, the significant overlaps suggest that they are part of a continuous disease spectrum. Recent genetic discoveries support this idea because mutations in a few genes (α-synuclein, LRRK2, tau) can cause partially overlapping pathologies. Additionally, mutations in causative genes and environmental toxins identify protein homeostasis and the mitochondria as key mediators of degeneration of dopaminergic circuits in the basal ganglia. The evolving mechanistic insight into the pathophysiology of PD and related conditions will contribute to the development of targeted and effective symptomatic treatments into disease-modifying therapies that will reduce the burden of these dreadful conditions.