Parkinson disease.
Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability. The underlying molecular pathogenesis involves multiple pathways and mechanisms: α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport and neuroinflammation. Recent research into diagnostic biomarkers has taken advantage of neuroimaging in which several modalities, including PET, single-photon emission CT (SPECT) and novel MRI techniques, have been shown to aid early and differential diagnosis. Treatment of Parkinson disease is anchored on pharmacological substitution of striatal dopamine, in addition to non-dopaminergic approaches to address both motor and non-motor symptoms and deep brain stimulation for those developing intractable L-DOPA-related motor complications. Experimental therapies have tried to restore striatal dopamine by gene-based and cell-based approaches, and most recently, aggregation and cellular transport of α-synuclein have become therapeutic targets. One of the greatest current challenges is to identify markers for prodromal disease stages, which would allow novel disease-modifying therapies to be started earlier.
Department of Neurology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
Werner
W
Poewe
Department of Neurology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
Klaus
K
Seppi
Parkinson's Disease Research Education and Clinical Center, San Francisco Veteran's Affairs Medical Center, San Francisco, California, USA.|Department of Neurology, University of California - San Francisco, San Francisco, California, USA.
Caroline M
CM
Tanner
Brain and Mind Centre, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.|Faculty of Medicine, University of New South Wales &Neuroscience Research Australia, Sydney, New South Wales, Australia.
Glenda M
GM
Halliday
Van Andel Research Institute, Center for Neurodegenerative Science, Grand Rapids, Michigan, USA.
Patrik
P
Brundin
Department of Neurology, University Hospital of Würzburg, Würzburg, Germany.
Jens
J
Volkmann
Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK.
Anette-Eleonore
AE
Schrag
Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Anthony E
AE
Lang
D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D018491:Dopamine Agonists / Q000494:pharmacology / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology*; D011788:Quality of Life / Q000523:psychology; D051844:alpha-Synuclein / Q000378:metabolism
D000978:Antiparkinson Agents; D015415:Biomarkers; D018491:Dopamine Agonists; D051844:alpha-Synuclein; D007980:Levodopa