Antiparkinsonian Drugs and Their Neuroprotective Effects.

Kitamura, Yoshihisa; Kakimura, Jun-ichi; Taniguchi, Takashi

doi:10.1248/bpb.25.284

Cited by 21 publications

(16 citation statements)

References 93 publications

(124 reference statements)

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“…Numerous neuropathological studies have shown that clinical signs of PD develop when more than 80% of DA neurons are lost. The content of DA neurons in the corpus striatum (the caudate nucleus and the putamen) considerably decreases in PD [28]. It is important to note that DA, glutamic acid, and acetylcholine (AC) regulate the activity of γ -aminobutyric acid receptors in the corpus striatum.…”

Section: Genetic Factors Affecting Parkinson's Disease and The Efficimentioning

confidence: 99%

“…Without going into details, the antiapoptotic proteins Bcl-2 and Bcl-x suppress the release of proapoptotic cytochrome c from mitochondria into the cytosol. The level of Bcl-2 is regulated in the brain [18]. Neurons with low-level expression of Bcl-2 are more susceptible to apoptosis.…”

Section: Genetic Factors Affecting Parkinson's Disease and The Efficimentioning

confidence: 99%

“…Then, cytochrome c activates the intermediates apoptosis protease-activating factor 1 (Apaf-1) and caspase 9, which, in turn, activates caspase 3 and several other caspases, eventually causing cell death. In addition, the antiapoptotic protein Bcl-2 induces differentiation of neurons and expedites axon regeneration in mammalian neurons [18]. Thus, apoptosis is regulated at several levels.…”

Section: Genetic Factors Affecting Parkinson's Disease and The Efficimentioning

confidence: 99%

“…A straightforward approach is to increase the DA and L-DOPA concentrations in the substantia nigra. However, both DA and L-DOPA exert a neurotoxic effect in vitro [18]. L-DOPA has been used as the main drug in PD for a long time.…”

Section: Pharmacokinetic Factors Metabolic Transformation Of Dopaminmentioning

confidence: 99%

“…Recent achievements in pharmacogenomics and pharmacogenetics have inspired new interest in the genetic predisposition to various NDs and the role of genetics in the efficiency of their treatment. It was believed until recently that the contribution of genetic predisposition, among all causal factors, to the development of parkinsonism was no more than 5% [18]. However, the data accumulated to date suggest a combined pathogenesis of parkinsonism: various associated disorders and factors-atherosclerosis, infections, neurotoxins, tumors, injuries, etc.-only trigger the clinical manifestation of parkinsonism, while the major role in its development is played by initial defects of basal ganglia [19,20].…”

mentioning

confidence: 99%

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Neurodegenerative Disorders: The Role of Genetic Factors in Their Origin and the Efficiency of Treatment

2005

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The review considers the main molecular physiological causes of neurodegenerative disorders. The genetic factors involved in Parkinson's and Alzheimer's diseases are conventionally divided into pharmacodynamic and pharmacokinetic. The former are analyzed at the levels of dopamine (DA) neurons and polymorphism of the D 1 , D 2 , and D 3 DA receptors. The role of polymorphisms of some proteins such as parkin (PARK1-PARK10) and α -synuclein in generation of Lewy bodies is described. The pharmacokinetic factors play a role in Parkinson's disease (PD) at the level of metabolism of DA, dioxyphenylalanine, and tyrosine and include polymorphisms of enzymes and proteins involved in the relevant metabolic reactions. The profile of DA metabolites may contribute to neurotoxicity and the development of PD. Prospects of drug therapy of PD and the risk of adverse drug effects such as mental disorders and dyskinesia are considered in terms of polymorphisms of enzymes and transport proteins.

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Section: Genetic Factors Affecting Parkinson's Disease and The Efficimentioning

confidence: 99%

Section: Genetic Factors Affecting Parkinson's Disease and The Efficimentioning

confidence: 99%

Section: Genetic Factors Affecting Parkinson's Disease and The Efficimentioning

confidence: 99%

Section: Pharmacokinetic Factors Metabolic Transformation Of Dopaminmentioning

confidence: 99%

mentioning

confidence: 99%

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Neurodegenerative Disorders: The Role of Genetic Factors in Their Origin and the Efficiency of Treatment

2005

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Neuroprotection in Parkinson Disease

Simpkins

Jankovic²

2003

Arch Intern Med

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Treatment of Parkinson disease has improved dramatically over the past quarter of a century and promising therapies are emerging. Although treatment with levodopa results in marked symptomatic improvement, mortality rates of the disease have remained relatively unchanged. Recent findings of abnormal protein folding, coupled with oxidative stress, provide scientific rationale for novel therapeutic strategies designed to slow disease progression. To be effective, these disease-modifying and neuroprotective therapies must be instituted early in the course of the disease and early diagnosis therefore is critical. Consequently, primary care physicians will play an increasingly important role in early institution of such neuroprotective strategies. This review is designed to highlight some of the recent advances in our understanding of the mechanisms of neurodegeneration and to draw attention to the importance of early recognition and implementation of the new therapeutic interventions.

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