Parkinson's Disease Mechanisms and Models

  title={Parkinson's Disease Mechanisms and Models},
  author={William T. Dauer and Serge Przedborski},

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Neuronal pathology in Parkinson’s disease

Dysfunction of the ubiquitin-proteasome pathway, protein aggregation, mitochondrial dysfunction, oxidative stress, activation of the c-Jun N-terminal kinase pathway, and inflammation have all been identified as important pathways leading to excitotoxic and apoptotic death of dopaminergic neurons.

Pathogenesis of nigral cell death in Parkinson's disease.

Neurodegenerative signaling factors and mechanisms in Parkinson's pathology.

Parkinson's disease: A Review about Pathogenesis, Pharmaceutical Treatment and Experimental Models

The primary drug for PD treatment is L-dopa; however, drug-induced dyskinesia and motor complications restricted its use as long term treatment, and dopamine agonists are alternative options for initial treatment of PD and have been reported to retard the onset of motor complications.

Parkinson’s disease: animal models and dopaminergic cell vulnerability

A summary of current knowledge about the different in vivo models of PD that are used in relation to the vulnerability of the dopaminergic neurons in the midbrain in the pathogenesis of PD is provided.

Cellular and Molecular Mechanisms of Parkinson’s Disease: Neurotoxins, Causative Genes, and Inflammatory Cytokines

Accumulating evidences points to a hypothesis that multiple primary causes of PD may be ultimately linked to a final common signal-transduction pathway leading to programmed cell death, i.e., apoptosis or autophagy, of the CA neurons.

Molecular pathophysiology of Parkinson's disease.

Increasing evidence indicates that deficits in mitochondrial function, oxidative and nitrosative stress, the accumulation of aberrant or misfolded proteins, and ubiquitin-proteasome system dysfunction may represent the principal molecular pathways or events that commonly underlie the pathogenesis of sporadic and familial forms of PD.

Animal Models of Parkinson’s Disease

The biochemical and cellular changes that occur following administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in rodents or monkeys are remarkably similar to those seen in idiopathic PD.

Ubiquitin-proteasome system dysfunction in experimental models of Parkinson's disease

The results suggest that UPS impairment consequent to neurotoxin exposure plays a crucial contributory role in dopaminergic degeneration and that exposure to neurotoxic agents and gene-environment interactions could elicit dopamergic neurotoxicity by converging to impair UPS function.

Animal Models of Parkinson’s Disease

In this chapter, a summary of the most used PD animal models are provided, including their advantages and limitations, including those related to α‐syn, PINK1, Parkin, DJ‐1, and LRRK2.



p53 inhibitors preserve dopamine neurons and motor function in experimental parkinsonism

It is reported that two novel synthetic inhibitors of the tumor suppressor protein p53, pifithrin‐α (PFT‐α) and Z‐1‐117, are highly effective in protecting midbrain dopaminergic neurons and improving behavioral outcome in a mouse model of Parkinson's disease.

Resistance of α-synuclein null mice to the parkinsonian neurotoxin MPTP

It is shown that α-synuclein null mice display striking resistance to MPTP-induced degeneration of DA neurons and DA release, and this resistance appears to result from an inability of the toxin to inhibit complex I.

Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease

Quantitative analysis of neuromelanin-pigmented neurons in control and parkinsonian midbrains demonstrates that the dopamine-containing cell groups of the normal human midbrain differ markedly from each other in the percentage of neurmelan in-pIGmented neurons they contain, and suggests a selective vulnerability of the neuromelsin- pigmented subpopulation of dopamine- containing mesencephalic neurons in Parkinson's disease.

Environmental Risk Factors and Parkinson's Disease: Selective Degeneration of Nigral Dopaminergic Neurons Caused by the Herbicide Paraquat

Findings unequivocally show that selective dopaminergic degeneration, one of the pathological hallmarks of PD, is also a characteristic of paraquat neurotoxicity.

Parkinson's disease

Evaluating the mesolimbic dopamine system in PD by counting pigmented neurons in the VTA contralateral to therapeutic lesions placed in the basal ganglia or thalamus found that VTA neurons were depleted to 36 to 55% of control values.

An In Vitro Model of Parkinson's Disease: Linking Mitochondrial Impairment to Altered α-Synuclein Metabolism and Oxidative Damage

These studies indicate that chronic low-grade complex I inhibition caused by rotenone exposure induces accumulation and aggregation of α-synuclein and ubiquitin, progressive oxidative damage, and caspase-dependent death, mechanisms that may be central to PD pathogenesis.

Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease.

Caspase-3 is an effector of apoptosis in experimental models of Parkinson's disease (PD). However, its potential role in the human pathology remains to be demonstrated. Using caspase-3

Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis.

Parkinson's disease (PD) is a common progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra. Although mutations in alpha-synuclein have been

Chaperone Suppression of α-Synuclein Toxicity in a Drosophila Model for Parkinson's Disease

Direct expression of the molecular chaperone Hsp70 prevented dopaminergic neuronal loss associated with α-synuclein in Drosophila and that interference with endogenous chaper one activity accelerated α- synuclein toxicity, suggesting chaperones may play a role in Parkinson's disease progression.