Rare genetic mutations shed light on the pathogenesis of Parkinson disease

Dawson, Ted M.; Dawson, Valina L.

doi:10.1172/jci200317575

Cited by 180 publications

(60 citation statements)

References 68 publications

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“…Hereditary mutations in the ER-associated E3 ubiquitin ligase Parkin have also been associated with ER stress-induced cell death and are found in patients with familial Parkinson disease (PD) (106,107). Overexpression of wild-type Parkin suppresses cell death induced by several ER stress-inducing agents, and by α-synuclein, the principal component of pathological Lewy bodies seen in PD (107).…”

Section: Er Stress and Diseasesmentioning

confidence: 99%

Endoplasmic reticulum stress: cell life and death decisions

Bailly-Maître²,

Reed³

2005

Journal of Clinical Investigation

2,068

1,763

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Disturbances in the normal functions of the ER lead to an evolutionarily conserved cell stress response, the unfolded protein response, which is aimed initially at compensating for damage but can eventually trigger cell death if ER dysfunction is severe or prolonged. The mechanisms by which ER stress leads to cell death remain enigmatic, with multiple potential participants described but little clarity about which specific death effectors dominate in particular cellular contexts. Important roles for ER-initiated cell death pathways have been recognized for several diseases, including hypoxia, ischemia/reperfusion injury, neurodegeneration, heart disease, and diabetes.

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Section: Er Stress and Diseasesmentioning

confidence: 99%

Endoplasmic reticulum stress: cell life and death decisions

Bailly-Maître²,

Reed³

2005

Journal of Clinical Investigation

2,068

1,763

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“…The effect of the cannabinoids on motor activity depends on the impact of the endocannabinoid system on the dopaminergic, glutamatergic, and GABAergic signaling systems throughout the basal ganglia [112, 136]. The high density of cannabinoid, dopamine, and vanilloid-like receptors coupled with ECBs within the basal ganglia and cerebellum suggests a potential therapeutic role for the cannabinoids in the control of voluntary movement and in movement disorders such as Parkinson's disease [98, 99, 121, 137]. Additional indications of an important role of the endocannabinoid system in the control of movement involve an inhibitory action of cannabinoids through fine tuning of various classical neurotransmitters activity [138], prominent changes in transmission of ECBs in the basal ganglia [139], and alteration of the CB1 binding as well as CB1 availability in the substantia nigra [85, 112, 119, 120, 140, 141].…”

Section: Cannabinoids and Parkinson's Diseasementioning

confidence: 99%

Marijuana Compounds: A Nonconventional Approach to Parkinson’s Disease Therapy

Babayeva

Assefa

Basu

et al. 2016

Parkinson's Disease

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Parkinson's disease (PD), a neurodegenerative disorder, is the second most common neurological illness in United States. Neurologically, it is characterized by the selective degeneration of a unique population of cells, the nigrostriatal dopamine neurons. The current treatment is symptomatic and mainly involves replacement of dopamine deficiency. This therapy improves only motor symptoms of Parkinson's disease and is associated with a number of adverse effects including dyskinesia. Therefore, there is unmet need for more comprehensive approach in the management of PD. Cannabis and related compounds have created significant research interest as a promising therapy in neurodegenerative and movement disorders. In this review we examine the potential benefits of medical marijuana and related compounds in the treatment of both motor and nonmotor symptoms as well as in slowing the progression of the disease. The potential for cannabis to enhance the quality of life of Parkinson's patients is explored.

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“…For example, PARK proteins are implicated in synaptic function (PARK1/α‐synuclein), protein degradation (PARK2/parkin, PARK9/ATP13A2, and PARK5/UCHL‐1), signal transduction (PARK8/LRRK2 and PARK11/GIGYF2), and protection against mitochondrial/oxidative stress (PARK6/PINK1, PARK7/DJ‐1, and PARK13/HTRA2). Collectively, malfunctions in these cellular mechanisms may prompt the onset and progression of PD; limited therapeutic interventions are available, despite being the second most common neurodegenerative disease (Dauer and Przedborski,2003; Dawson and Dawson,2003; Fahn,2003).…”

Section: Introductionmentioning

confidence: 99%

C. elegans as a model organism to investigate molecular pathways involved with Parkinson's disease

Harrington

Hamamichi

Caldwell

et al. 2010

Developmental Dynamics

125

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Parkinson's disease (PD) is an age-related movement disorder resulting, in part, from selective loss of dopaminergic neurons. Both invertebrate and mammalian models have been developed to study the cellular mechanisms altered during disease progression; nevertheless there are limitations within each model. Mammalian models remain invaluable in studying PD, but are expensive and time consuming. Here, we review genetic and environmental factors associated with PD, and describe how the nematode roundworm, Caenorhabditis elegans, has been used as a model organism for studying various aspects of this neurodegenerative disease. Both genetic and chemical screens have been conducted in C. elegans to identify molecular pathways, proteins, and small molecules that can impact PD pathology. Lastly, we highlight future areas of investigation, in the context of emerging fields in biology, where the nematode can be exploited to provide mechanistic insights and potential strategies to accelerate the path toward possible therapeutic intervention for PD. Developmental Dynamics 239:1282-1295,

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Rare genetic mutations shed light on the pathogenesis of Parkinson disease

Cited by 180 publications

References 68 publications

Endoplasmic reticulum stress: cell life and death decisions

Endoplasmic reticulum stress: cell life and death decisions

Marijuana Compounds: A Nonconventional Approach to Parkinson’s Disease Therapy

C. elegans as a model organism to investigate molecular pathways involved with Parkinson's disease

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