Etiology and pathogenesis of Parkinson's disease.

  title={Etiology and pathogenesis of Parkinson's disease.},
  author={C. Warren Olanow and William G. Tatton},
  journal={Annual review of neuroscience},
Parkinson's disease (PD) is an age-related neurodegenerative disorder that affects approximately 1 million persons in the United States. It is characterized by resting tremor, rigidity, bradykinesia or slowness, gait disturbance, and postural instability. Pathological features include degeneration of dopaminergic neurons in the substantia nigra pars compacta coupled with intracytoplasmic inclusions known as Lewy bodies. Neurodegeneration and Lewy bodies can also be found in the locus ceruleus… 

Neuropathology of Parkinson’s Disease

Parkinson’s disease is a progressive multiorgan proteinopathy caused by misfolded α-synuclein (α-syn) with variegated motor and nonmotor symptoms owing to a spreading process of synaptic and neuronal loss.

Recent developments in the pathology of Parkinson's disease.

  • K. Jellinger
  • Biology
    Journal of neural transmission. Supplementum
  • 2002
Experimental and tissue culture studies suggest that apoptosis, a genetically determined form of programmed cell death, represents the most common pathway in neurodegeneration, but DNA fragmentation, overexpression of proapoptotic proteins and activated caspase-3, the effector enzyme of the terminal apopoptic cascade, have only been detected in SN of PD brains.

Nonmotor symptom complex of Parkinson's disease--an under-recognized entity.

Since, NMS add significantly to the overall disability caused by PD, their early recognition and treatment may go a long way in improving the quality of life of PD patients as well as the economic burden on the carers.

Existing dopaminergic therapies for Parkinson's disease

A brief review on different dopamine receptor agonists has been presented and indirect dopaminergic agents, such as selective monoamine oxidase-B inhibitors and catechol-O-methyltransferase inhibitors, have also been included in the description.

The scientific basis for the current treatment of Parkinson's disease.

  • C. Olanow
  • Biology, Psychology
    Annual review of medicine
  • 2004
Insights into the organization of the basal ganglia in the normal and PD conditions has permitted the design of new treatment strategies that reduce the risk of developing motor complications and the development of putative neuroprotective drugs that might slow or stop disease progression.

Advances in genetic models of Parkinson's disease

Multiple system atrophy

This Primer by Poewe and colleagues summarizes the epidemiology, diagnosis, pathophysiology and treatment of multiple system atrophy and provides an overview of the quality of life issues faced by patients with this disorder and future research avenues.

Inflammation and dopaminergic neuronal loss in Parkinson's disease: a complex matter


Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia

The altered GSH/GSSG ratio in the substantia nigra in Parkinson's disease is consistent with the concept of oxidative stress as a major component in the pathogenesis of nigral cell death in Parkinson’s disease.

Autosomal dominant parkinson's disease and α‐synuclein

Mutation analysis of the α‐synuclein in four unrelated families with PD revealed a missense mutation segregating with the illness, which may offer new insights in the understanding of the pathways that lead to neuronal degeneration.

Understanding cell death in parkinson's disease

Evidence enables us to hypothesize that a failure to process structurally modified proteins in regions of the brain exhibiting oxidative stress is a cause of both familial and sporadic PD.

α-Synuclein in Lewy bodies

Strong staining of Lewy bodies from idiopathic Parkinson's disease with antibodies for α-synuclein, a presynaptic protein of unknown function which is mutated in some familial cases of the disease, indicates that the LewY bodies from these two diseases may have identical compositions.

Do environmental toxins cause Parkinson's disease? A critical review

PD will be considered a distinct clinical and neuro Pathologic entity, with a characteristic natural history and well-defined neuropathologic features, including the loss of pigmented neurons in the substantia nigra and the presence of Lewy bodies.

Subthalamic nucleus‐mediated excitotoxicity in parkinson's disease: A target for neuroprotection

It is proposed that pharmacologic or surgical therapies that reduce STN neuronal overactivity or block glutamate receptors in the SNc and other target structures might be neuroprotective and might slow or halt the progression of neurodegeneration in PD.

Primate models of movement disorders of basal ganglia origin

  • M. DeLong
  • Psychology, Biology
    Trends in Neurosciences
  • 1990

Indices of oxidative stress and mitochondrial function in individuals with incidental Lewy body disease

The marked reduction in nigral reduced glutathione levels suggests this to be an important early change in the process of oxidative stress underlying Parkinson's disease.

Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses?

  • M. Beal
  • Biology
    Annals of neurology
  • 1992
If defective mitochondrial energy metabolism plays a role in cell death in neurodegenerative disorders, potential therapeutic strategies would be to use excitatory amino acid antagonists or agents to bypass bioenergetic defects.

Progressive Changes in Striatal Dopaminergic Markers, Nigral Volume, and Rotational Behavior Following Iron Infusion into the Rat Substantia Nigra

Data indicate that a single exposure of the SN to a modest amount of Fe can induce persistent/progressive changes occurring through a number of months postinfusion and further establishes intranigral Fe infusion as an animal model for PD.