scholarly journals Cannabis Dopaminergic Effects Induce Hallucinations in a Patient with Parkinson’s Disease

Medicina ◽  
2021 ◽  
Vol 57 (10) ◽  
pp. 1107
Author(s):  
Katie Pizzolato ◽  
David Thacker ◽  
Nicole Del Toro-Pagán ◽  
Abeer Hanna ◽  
Jacques Turgeon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Chronic Back Pain ◽  
Therapeutic Agents ◽  
Cannabis Use ◽  
Patient Case ◽  
Psychoactive Effects ◽  
Medicinal Cannabis ◽  
The Brain

Cannabis products that contain the tetrahydrocannabinol (THC) cannabinoid are emerging as promising therapeutic agents for the treatment of medical conditions such as chronic pain. THC elicits psychoactive effects through modulation of dopaminergic neurons, thereby altering levels of dopamine in the brain. This case report highlights the complexity associated with medicinal cannabis and the health risks associated with its use. A 57-year-old male with Parkinson’s disease was experiencing worsening tremors and vivid hallucinations despite therapy optimization attempts. It was discovered that the patient took cannabis for chronic back pain, and a pharmacogenomics (PGx) test indicated the presence of variants for the COMT and HTR2A genes. These variants could increase dopamine levels and predispose patients to visual hallucinations. Once the cannabis was discontinued, the patient’s hallucinations began to slowly dissipate. Cannabis use continues to expand as it gains more acceptance legally and medicinally, but cannabis can affect the response to drugs. This patient case suggests that cannabis use in combination with dopamine-promoting drugs, especially in a patient with genetic variants, can increase the risk for vivid hallucinations. These conditions support the importance of considering herb–drug interactions and PGx data when performing a medication safety review.

Comparison of Cytocidal Activities of L-DOPA and Dopamine in S. cerevisiae and C. glabrata

2020 ◽  
Vol 16 (1) ◽  
pp. 90-93
Author(s):  
Carmen E. Iriarte ◽  
Ian G. Macreadie
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Candida Glabrata ◽  
High Sensitivity ◽  
Time Dependent ◽  
Colony Forming Units ◽  
Dependent Cell ◽  
The Brain

Background: Parkinson's Disease results from a loss of dopaminergic neurons, and reduced levels of the neurotransmitter dopamine. Parkinson's Disease treatments involve increasing dopamine levels through administration of L-DOPA, which can cross the blood brain barrier and be converted to dopamine in the brain. The toxicity of dopamine has previously studied but there has been little study of L-DOPA toxicity. Methods: We have compared the toxicity of dopamine and L-DOPA in the yeasts, Saccharomyces cerevisiae and Candida glabrata by cell viability assays, measuring colony forming units. Results: L-DOPA and dopamine caused time-dependent cell killing in Candida glabrata while only dopamine caused such effects in Saccharomyces cerevisiae. The toxicity of L-DOPA is much lower than dopamine. Conclusion: Candida glabrata exhibits high sensitivity to L-DOPA and may have advantages for studying the cytotoxicity of L-DOPA.

scholarly journals Leucine-Rich Repeat Kinase 2 in Parkinson’s Disease: Updated from Pathogenesis to Potential Therapeutic Target

2018 ◽  
Vol 79 (5-6) ◽  
pp. 256-265 ◽  
Author(s):  
Jinhua Chen ◽  
Ying Chen ◽  
Jiali Pu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Significant Role ◽  
Dopaminergic Neurons ◽  
Recent Progress ◽  
Therapeutic Agents ◽  
Leucine Rich Repeat ◽  
Potential Therapeutic Target ◽  
Genetic And Environmental Factors

Background: Parkinson’s disease (PD) is characterized by the selective loss of dopaminergic neurons in the midbrain. The pathogenesis of PD is not fully understood but is likely caused by a combination of genetic and environmental factors. Several genes are associated with the onset and progression of familial PD. There is increasing evidence that leucine-rich repeat kinase 2 (LRRK2) plays a significant role in PD pathophysiology. Summary: Many studies have been conducted to elucidate the functions of LRRK2 and identify effective LRRK2 inhibitors for PD treatment. In this review, we discuss the role of LRRK2 in PD and recent progress in the use of LRRK2 inhibitors as therapeutic agents. Key Messages: LRRK2 plays a significant role in the pathophysiology of PD, and pharmacological inhibition of LRRK2 has become one of the most promising potential therapies for PD. Further research is warranted to determine the functions of LRRK2 and expand the applications of LRRK2 inhibitors in PD treatment.

Parkinson's Disease

2019 ◽  
pp. 252-273 ◽  
Author(s):  
Vaibhav Walia ◽  
Ashish Gakkhar ◽  
Munish Garg
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Older Patients ◽  
Neurodegenerative Disorder ◽  
Progressive Loss ◽  
The Brain

Parkinson's disease (PD) is a neurodegenerative disorder in which a progressive loss of the dopaminergic neurons occurs. The loss of the neurons is most prominent in the substantia nigra region of the brain. The prevalence of PD is much greater among the older patients suggesting the risk of PD increases with the increase of age. The exact cause of the neurodegeneration in PD is not known. In this chapter, the authors introduce PD, demonstrate its history, pathogenesis, neurobiology, sign and symptoms, diagnosis, and pharmacotherapy.

scholarly journals Association Between Decreased Srpk3 Expression And An Increase In Substantia Nigra Alpha-Synuclein Levels In An MPTP-Induced Parkinson’s Disease Mouse Model

2022 ◽  
Author(s):  
Min Hyung Seo ◽  
Sujung Yeo
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Cell Loss ◽  
Alpha Synuclein ◽  
Mice Model ◽  
Dopaminergic Cell ◽  
The Brain

Abstract Parkinson’s disease (PD) is known as the second most common neurodegenerative disease, which is caused by destruction of dopaminergic neurons in the substantia nigra (SN) of the brain; however, the reason for the death of dopaminergic neurons remains unclear. An increase in α-synuclein (α-syn) is considered an important factor in the pathogenesis of PD. In the current study, we investigated the association between PD and serine/arginine-rich protein specific kinase 3 (Srpk3) in MPTP-induced parkinsonism mice model and in SH-SY5Y cells treated with MPP+. Srpk3 expression was significantly downregulated, while tyrosine hydroxylase (TH) decreased and α-synuclein (α-syn) increased after 4 weeks of MPTP intoxication treatment. Dopaminergic cell reduction and α-syn increase were demonstrated by inhibiting Srpk3 expression by siRNA in SH-SY5Y cells. Moreover, a decrease in Srpk3 expression upon siRNA treatment promoted dopaminergic cell reduction and α-syn increase in SH-SY5Y cells treated with MPP+. These results suggest that the decrease in Srpk3 expression due to Srpk3 siRNA caused both a decrease in TH and an increase in α-syn. This raises new possibilities for studying how Srpk3 controls dopaminergic cells and α-syn expression, which may be related to the pathogenesis of PD. Our results provide an avenue for understanding the role of Srpk3 during dopaminergic cell loss and α-syn increase in the SN. Furthermore, this study could support a therapeutic possibility for PD in that the maintenance of Srpk3 expression inhibited dopaminergic cell reduction.

scholarly journals Dysregulation of the AP2M1 phosphorylation cycle by LRRK2 impairs endocytosis and leads to dopaminergic neurodegeneration

2021 ◽  
Vol 14 (693) ◽  
pp. eabg3555
Author(s):  
Qinfang Liu ◽  
Judith Bautista-Gomez ◽  
Daniel A. Higgins ◽  
Jianzhong Yu ◽  
Yulan Xiong
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Adaptor Protein ◽  
Endocytic Trafficking ◽  
Dopaminergic Neurodegeneration ◽  
Lrrk2 G2019s ◽  
Endocytic Machinery ◽  
Mutant Lrrk2 ◽  
The Brain

Mutations in the kinase LRRK2 and impaired endocytic trafficking are both implicated in the pathogenesis of Parkinson’s disease (PD). Expression of the PD-associated LRRK2 mutant in mouse dopaminergic neurons was shown to disrupt clathrin-mediated endocytic trafficking. Here, we explored the molecular mechanism linking LRRK2 to endocytosis and found that LRRK2 bound to and phosphorylated the μ2 subunit of the adaptor protein AP2 (AP2M1), a core component of the clathrin-mediated endocytic machinery. Analysis of human SH-SY5Y cells and mouse neurons and tissues revealed that loss of LRRK2 abundance or kinase function resulted in decreased phosphorylation of AP2M1, which is required for the initial formation of clathrin-coated vesicles (CCVs). In contrast, overexpression of LRRK2 or expression of a Parkinson’s disease–associated gain-of-function mutant LRRK2 (G2019S) inhibited the uncoating of AP2M1 from CCVs at later stages and prevented new cycles of CCV formation. Thus, the abundance and activity of LRRK2 must be calibrated to ensure proper endocytosis. Dysregulated phosphorylation of AP2M1 from the brain but not thyroid tissues of LRRK2 knockout and G2019S-knockin mice suggests a tissue-specific regulatory mechanism of endocytosis. Furthermore, we found that LRRK2-dependent phosphorylation of AP2M1 mediated dopaminergic neurodegeneration in a Drosophila model of PD. Together, our findings provide a mechanistic link between LRRK2, AP2, and endocytosis in the pathogenesis of PD.

Role of α-synuclein in neurodegeneration: implications for the pathogenesis of Parkinson's disease

2014 ◽  
Vol 56 ◽  
pp. 125-135 ◽  
Author(s):  
Shun Yu ◽  
Piu Chan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Experimental Studies ◽  
Research Progress ◽  
Pathogenic Role ◽  
Normal Expression ◽  
The Brain ◽  
Recent Research Progress

α-Syn (α-synuclein) is a small soluble acidic protein that is extensively expressed in the nervous system. Genetic, clinical and experimental studies demonstrate that α-syn is strongly implicated in the pathogenesis of PD (Parkinson's disease). However, the pathogenic mechanism remains elusive. In the present chapter, we first describe the normal expression and potential physiological functions of α-syn. Then, we introduce recent research progress related to the pathogenic role of α-syn in PD, with special emphasis on how α-syn oligomers cause the preferential degeneration of dopaminergic neurons in the substantia nigra and the spreading of α-syn pathology in the brain of PD patients.

scholarly journals Monoamine Reuptake Inhibitors in Parkinson’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-71 ◽  
Author(s):  
Philippe Huot ◽  
Susan H. Fox ◽  
Jonathan M. Brotchie
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic System ◽  
Therapeutic Agents ◽  
Review Article ◽  
Monoamine Transporters ◽  
Noradrenergic Neurons ◽  
The Brain ◽  
Selective Dopamine ◽  
Monoamine Reuptake Inhibitors

The motor manifestations of Parkinson’s disease (PD) are secondary to a dopamine deficiency in the striatum. However, the degenerative process in PD is not limited to the dopaminergic system and also affects serotonergic and noradrenergic neurons. Because they can increase monoamine levels throughout the brain, monoamine reuptake inhibitors (MAUIs) represent potential therapeutic agents in PD. However, they are seldom used in clinical practice other than as antidepressants and wake-promoting agents. This review article summarises all of the available literature on use of 50 MAUIs in PD. The compounds are divided according to their relative potency for each of the monoamine transporters. Despite wide discrepancy in the methodology of the studies reviewed, the following conclusions can be drawn: (1) selective serotonin transporter (SERT), selective noradrenaline transporter (NET), and dual SERT/NET inhibitors are effective against PD depression; (2) selective dopamine transporter (DAT) and dual DAT/NET inhibitors exert an anti-Parkinsonian effect when administered as monotherapy but do not enhance the anti-Parkinsonian actions of L-3,4-dihydroxyphenylalanine (L-DOPA); (3) dual DAT/SERT inhibitors might enhance the anti-Parkinsonian actions of L-DOPA without worsening dyskinesia; (4) triple DAT/NET/SERT inhibitors might exert an anti-Parkinsonian action as monotherapy and might enhance the anti-Parkinsonian effects of L-DOPA, though at the expense of worsening dyskinesia.

scholarly journals Viral vector delivery of neurotrophic factors for Parkinson's disease therapy

2015 ◽  
Vol 17 ◽  
Author(s):  
Martin J. Kelly ◽  
Gerard W. O'Keeffe ◽  
Aideen M. Sullivan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Neurotrophic Factors ◽  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Viral Vectors ◽  
Viral Vector ◽  
Neurodegenerative Disorder ◽  
The Brain

Parkinson's disease (PD) is a neurodegenerative disorder characterised by the progressive loss of midbrain dopaminergic neurons, which causes motor impairments. Current treatments involve dopamine replacement to address the disease symptoms rather than its cause. Factors that promote the survival of dopaminergic neurons have been proposed as novel therapies for PD. Several dopaminergic neurotrophic factors (NTFs) have been examined for their ability to protect and/or restore degenerating dopaminergic neurons, both in animal models and in clinical trials. These include glial cell line-derived neurotrophic factor, neurturin, cerebral dopamine neurotrophic factor and growth/differentiation factor 5. Delivery of these NTFs via injection or infusion to the brain raises several practical problems. A new delivery approach for NTFs involves the use of recombinant viral vectors to enable long-term expression of these factors in brain cells. Vectors used include those based on adenoviruses, adeno-associated viruses and lentiviruses. Here we review progress to date on the potential of each of these four NTFs as novel therapeutic strategies for PD, as well as the challenges that have arisen, from pre-clinical analysis to clinical trials. We conclude by discussing recently-developed approaches to optimise the delivery of NTF-carrying viral vectors to the brain.

Effect of Myricetin on the Loss of Dopaminergic Neurons in the Transgenic Drosophila Model of Parkinson’s Disease

2019 ◽  
Vol 14 (1) ◽  
pp. 58-64 ◽  
Author(s):  
Gulshan Ara ◽  
Mohammad Afzal ◽  
Smita Jyoti ◽  
Falaq Naz ◽  
Rahul ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Neuronal Damage ◽  
Radical Scavenging ◽  
Lewy Bodies ◽  
Dopamine Content ◽  
Drosophila Model ◽  
Dose Dependent ◽  
The Brain

Background: The formation of Lewy bodies is associated with the production of reactive oxygen species (ROS) and the neuronal damage specifically the dopaminergic neurons in the Parkinson’s disease patients. Hence any agent that could curtail the production of ROS /oxidative stress could act as a possible therapeutic agent thereby preventing the neuronal damage. </P><P> Method: In the present study, we first evaluated the antioxidant potential of myricetin by performing superoxide anion scavenging and diphenyl-picrylhydrazyl (DPPH) free radical scavenging assays. Myricetin at a final concentration of 10, 20 and 40&#181;M was mixed in diet and the PD flies were allowed to feed on it for 24 days. After 24 days of exposure, the dopamine content was estimated in brain and the immunohistochemistry was performed for the tyroxine hydroxylase activity on the brain sections from each group. </P><P> Results: Myricetin showed a dose-dependent increase in the antioxidative activity. The exposure of PD flies to 10, 20 and 40&#181;M of Myricetin not only showed a dose-dependent significant increase in the dopamine content compared to unexposed PD flies (p<0.05), but also prevented the loss of dopaminergic neurons in the brain of PD flies. </P><P> Conclusion: The results suggest that the antioxidative potential of myricetin is responsible for preventing the loss of dopaminergic neurons and dopamine content.

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