scholarly journals Pesticides and Parkinson’s disease: A potential hazard in agricultural communities

2017 ◽  
Vol 5 (20) ◽  
pp. 60
Author(s):  
Smathorn Thakolwiboon ◽  
Parunyou Julayanont ◽  
Doungporn Ruthirago
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Synergistic Effects ◽  
Neuronal Loss ◽  
Ubiquitin Proteasome System ◽  
Alpha Synuclein ◽  
Current Evidence ◽  
Potential Hazard ◽  
Dopaminergic Neuronal Loss

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder. Its pathogenesis isrelated to both genetic and environmental factors. Current evidence suggests that pesticideexposure is one of the risk factors of PD. In this review, we summarize four molecularmechanisms of pesticide-induced PD with supportive evidences from both laboratory andepidemiological studies. Rotenone is the first pesticide reported to be associated with PD byinhibiting complex I of mitochondrial electron transport chain. Paraquat, a commonly-usedherbicide in some countries, is an oxidative stressor causing dopaminergic neuronal loss whichcontributes to the pathogenesis of PD. The ubiquitin-proteasome system (UPS) and aldehydedehydrogenase (ALDH) inhibitors cause unwanted proteins (especially alpha-synuclein) and3,4-dihydroxyphenylacetaldehyde (DOPAL) accumulation leading to dopaminergic neuronalapoptosis. In addition, exposure to different pesticides affecting different mechanisms mayhave synergistic effects in increasing risk of PD. Protective glove use, the amount of fat intake,and neuroprotective agents are reported to have disease modification effects for pesticideassociatedPD.

scholarly journals Alpha-Synuclein Aggregation in Parkinson's Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
E. Srinivasan ◽  
G. Chandrasekhar ◽  
P. Chandrasekar ◽  
K. Anbarasu ◽  
A. S. Vickram ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Genetic Factors ◽  
Neurodegenerative Disorder ◽  
Neuronal Loss ◽  
Alpha Synuclein ◽  
Substantia Nigra Pars Compacta ◽  
Vulnerability Factors ◽  
Alpha Synuclein Aggregation

Parkinson's disease (PD), a neurodegenerative disorder characterized by distinct aging-independent loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) region urging toward neuronal loss. Over the decade, various key findings from clinical perspective to molecular pathogenesis have aided in understanding the genetics with assorted genes related with PD. Subsequently, several pathways have been incriminated in the pathogenesis of PD, involving mitochondrial dysfunction, protein aggregation, and misfolding. On the other hand, the sporadic form of PD cases is found with no genetic linkage, which still remain an unanswered question? The exertion in ascertaining vulnerability factors in PD considering the genetic factors are to be further dissevered in the forthcoming decades with advancement in research studies. One of the major proponents behind the prognosis of PD is the pathogenic transmutation of aberrant alpha-synuclein protein into amyloid fibrillar structures, which actuates neurodegeneration. Alpha-synuclein, transcribed by SNCA gene is a neuroprotein found predominantly in brain. It is implicated in the modulation of synaptic vesicle transport and eventual release of neurotransmitters. Due to genetic mutations and other elusive factors, the alpha-synuclein misfolds into its amyloid form. Therefore, this review aims in briefing the molecular understanding of the alpha-synuclein associated with PD.

scholarly journals Drosophila tubulin polymerization promoting protein mutants reveal pathological correlates relevant to human Parkinson’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jing Xie ◽  
Shuting Chen ◽  
Jean C. Bopassa ◽  
Swati Banerjee
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Structural Damage ◽  
Neurodegenerative Disorder ◽  
Neuronal Loss ◽  
In Vivo Studies ◽  
Tubulin Polymerization ◽  
Protein Mutants ◽  
Dopaminergic Neuronal Loss

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disorder with no known cure. PD is characterized by locomotion deficits, nigrostriatal dopaminergic neuronal loss, mitochondrial dysfunctions and formation of α-Synuclein aggregates. A well-conserved and less understood family of Tubulin Polymerization Promoting Proteins (TPPP) is also implicated in PD and related disorders, where TPPP exists in pathological aggregates in neurons in patient brains. However, there are no in vivo studies on mammalian TPPP to understand the genetics and neuropathology linking TPPP aggregation or neurotoxicity to PD. Recently, we discovered the only Drosophila homolog of human TPPP named Ringmaker (Ringer). Here, we report that adult ringer mutants display progressive locomotor disabilities, reduced lifespan and neurodegeneration. Importantly, our findings reveal that Ringer is associated with mitochondria and ringer mutants have mitochondrial structural damage and dysfunctions. Adult ringer mutants also display progressive loss of dopaminergic neurons. Together, these phenotypes of ringer mutants recapitulate some of the salient features of human PD patients, thus allowing us to utilize ringer mutants as a fly model relevant to PD, and further explore its genetic and molecular underpinnings to gain insights into the role of human TPPP in PD.

scholarly journals Alpha-Synuclein Induced Immune Cells Activation and Associated Therapy in Parkinson’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Ruichen Su ◽  
Tian Zhou
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Immune System ◽  
Immune Cells ◽  
Neurodegenerative Disorder ◽  
Alpha Synuclein ◽  
Autoimmune Response ◽  
T Helper ◽  
Helper Type

Parkinson’s disease (PD) is a neurodegenerative disorder closely related to immunity. An important aspect of the pathogenesis of PD is the interaction between α-synuclein and a series of immune cells. Studies have shown that accumulation of α-synuclein can induce an autoimmune response that accelerates the progression of PD. This study discusses the mechanisms underlying the interaction between α-synuclein and the immune system. During the development of PD, abnormally accumulated α-synuclein becomes an autoimmune antigen that binds to Toll-like receptors (TLRs) that activate microglia, which differentiate into the microglia type 1 (M1) subtype. The microglia activate intracellular inflammatory pathways, induce the release of proinflammatory cytokines, and promote the differentiation of cluster of differentiation 4 + (CD4 +) T cells into proinflammatory T helper type 1 (Th1) and T helper type 17 (Th17) subtypes. Given the important role of α-synuclein in the immune system of the patients with PD, identifying potential targets of immunotherapy related to α-synuclein is critical for slowing disease progression. An enhanced understanding of immune-associated mechanisms in PD can guide the development of associated therapeutic strategies in the future.

scholarly journals Amelioration of Mitochondrial Quality Control and Proteostasis by Natural Compounds in Parkinson’s Disease Models

2019 ◽  
Vol 20 (20) ◽  
pp. 5208 ◽  
Author(s):  
Bongki Cho ◽  
Taeyun Kim ◽  
Yu-Jin Huh ◽  
Jaemin Lee ◽  
Yun-Il Lee
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disorder ◽  
Ubiquitin Proteasome System ◽  
Natural Compounds ◽  
Cellular Damage ◽  
Pathophysiological Mechanism ◽  
Neuroprotective Effects ◽  
Age Related

Parkinson’s disease (PD) is a well-known age-related neurodegenerative disorder associated with longer lifespans and rapidly aging populations. The pathophysiological mechanism is a complex progress involving cellular damage such as mitochondrial dysfunction and protein homeostasis. Age-mediated degenerative neurological disorders can reduce the quality of life and also impose economic burdens. Currently, the common treatment is replacement with levodopa to address low dopamine levels; however, this does not halt the progression of PD and is associated with adverse effects, including dyskinesis. In addition, elderly patients can react negatively to treatment with synthetic neuroprotection agents. Recently, natural compounds such as phytochemicals with fewer side effects have been reported as candidate treatments of age-related neurodegenerative diseases. This review focuses on mitochondrial dysfunction, oxidative stress, hormesis, proteostasis, the ubiquitin‒proteasome system, and autophagy (mitophagy) to explain the neuroprotective effects of using natural products as a therapeutic strategy. We also summarize the efforts to use natural extracts to develop novel pharmacological candidates for treatment of age-related PD.

Dopaminergic neuronal loss in transgenic mice expressing the Parkinson's disease-associated UCH-L1 I93M mutant

2007 ◽  
Vol 50 (1) ◽  
pp. 119-129 ◽  
Author(s):  
Rieko Setsuie ◽  
Yu-Lai Wang ◽  
Hideki Mochizuki ◽  
Hitoshi Osaka ◽  
Hideki Hayakawa ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transgenic Mice ◽  
Neuronal Loss ◽  
Dopaminergic Neuronal Loss

scholarly journals Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic Neurodegeneration

2020 ◽  
Vol 21 (17) ◽  
pp. 5981
Author(s):  
Ola Wasel ◽  
Jennifer L. Freeman
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Dopaminergic System ◽  
Neuronal Loss ◽  
Dopaminergic Neurodegeneration ◽  
Biological Studies ◽  
Vertebrate Model ◽  
Dopaminergic Neuronal Loss ◽  
6 Hydroxydopamine

The zebrafish (Danio rerio) is routinely used in biological studies as a vertebrate model system that provides unique strengths allowing applications in studies of neurodevelopmental and neurodegenerative diseases. One specific advantage is that the neurotransmitter systems are highly conserved throughout vertebrate evolution, including between zebrafish and humans. Disruption of the dopaminergic signaling pathway is linked to multiple neurological disorders. One of the most common is Parkinson’s disease, a neurodegenerative disease associated with the loss of dopaminergic neurons, among other neuropathological characteristics. In this review, the development of the zebrafish’s dopaminergic system, focusing on genetic control of the dopaminergic system, is detailed. Second, neurotoxicant models used to study dopaminergic neuronal loss, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the pesticides paraquat and rotenone, and 6-hydroxydopamine (6-OHDA), are described. Next, zebrafish genetic knockdown models of dj1, pink1, and prkn established for investigating mechanisms of Parkinson’s disease are discussed. Chemical modulators of the dopaminergic system are also highlighted to showcase the applicability of the zebrafish to identify mechanisms and treatments for neurodegenerative diseases such as Parkinson’s disease associated with the dopaminergic system.

Sign in / Sign up

Export Citation Format

Share Document