scholarly journals Epigenetic Regulation of Neuroinflammation in Parkinson’s Disease

2021 ◽  
Vol 22 (9) ◽  
pp. 4956
Author(s):  
Madiha Rasheed ◽  
Junhan Liang ◽  
Chaolei Wang ◽  
Yulin Deng ◽  
Zixuan Chen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Glial Cells ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Dopamine Neurons ◽  
Epigenetic Mechanisms ◽  
Vicious Cycle ◽  
Motor Disability ◽  
Neuron Damage

Neuroinflammation is one of the most significant factors involved in the initiation and progression of Parkinson’s disease. PD is a neurodegenerative disorder with a motor disability linked with various complex and diversified risk factors. These factors trigger myriads of cellular and molecular processes, such as misfolding defective proteins, oxidative stress, mitochondrial dysfunction, and neurotoxic substances that induce selective neurodegeneration of dopamine neurons. This neuronal damage activates the neuronal immune system, including glial cells and inflammatory cytokines, to trigger neuroinflammation. The transition of acute to chronic neuroinflammation enhances the susceptibility of inflammation-induced dopaminergic neuron damage, forming a vicious cycle and prompting an individual to PD development. Epigenetic mechanisms recently have been at the forefront of the regulation of neuroinflammatory factors in PD, proposing a new dawn for breaking this vicious cycle. This review examined the core epigenetic mechanisms involved in the activation and phenotypic transformation of glial cells mediated neuroinflammation in PD. We found that epigenetic mechanisms do not work independently, despite being coordinated with each other to activate neuroinflammatory pathways. In this regard, we attempted to find the synergic correlation and contribution of these epigenetic modifications with various neuroinflammatory pathways to broaden the canvas of underlying pathological mechanisms involved in PD development. Moreover, this study highlighted the dual characteristics (neuroprotective/neurotoxic) of these epigenetic marks, which may counteract PD pathogenesis and make them potential candidates for devising future PD diagnosis and treatment.

scholarly journals Peptide TFP5/TP5 derived from Cdk5 activator P35 provides neuroprotection in the MPTP model of Parkinson’s disease

2015 ◽  
Vol 26 (24) ◽  
pp. 4478-4491 ◽  
Author(s):  
BK. Binukumar ◽  
Varsha Shukla ◽  
Niranjana D. Amin ◽  
Philip Grant ◽  
M. Bhaskar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Selective Inhibition ◽  
Motor Dysfunction ◽  
Dopamine Neurons ◽  
Dopamine Depletion ◽  
Neuroprotective Effects

Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopamine neurons in the substantia nigra, decreased striatal dopamine levels, and consequent extrapyramidal motor dysfunction. Recent evidence indicates that cyclin-dependent kinase 5 (Cdk5) is inappropriately activated in several neurodegenerative conditions, including PD. To date, strategies to specifically inhibit Cdk5 hyperactivity have not been successful without affecting normal Cdk5 activity. Previously we reported that TFP5 peptide has neuroprotective effects in animal models of Alzheimer’s disease. Here we show that TFP5/TP5 selective inhibition of Cdk5/p25 hyperactivation in vivo and in vitro rescues nigrostriatal dopaminergic neurodegeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP/MPP+) in a mouse model of PD. TP5 peptide treatment also blocked dopamine depletion in the striatum and improved gait dysfunction after MPTP administration. The neuroprotective effect of TFP5/TP5 peptide is also associated with marked reduction in neuroinflammation and apoptosis. Here we show selective inhibition of Cdk5/p25 ­hyperactivation by TFP5/TP5 peptide, which identifies the kinase as a potential therapeutic target to reduce neurodegeneration in Parkinson’s disease.

Emerging targets for the diagnosis of Parkinson’s disease: examination of systemic biomarkers

2021 ◽  
Author(s):  
Lara Cheslow ◽  
Adam E Snook ◽  
Scott A Waldman
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Unmet Need ◽  
Multiple Organ ◽  
The Body ◽  
Organ Systems ◽  
Diagnostic Approaches ◽  
New Biomarkers

Parkinson’s disease (PD) is a highly prevalent and irreversible neurodegenerative disorder that is typically diagnosed in an advanced stage. Currently, there are no approved biomarkers that reliably identify PD patients before they have undergone extensive neuronal damage, eliminating the opportunity for future disease-modifying therapies to intervene in disease progression. This unmet need for diagnostic and therapeutic biomarkers has fueled PD research for decades, but these efforts have not yet yielded actionable results. Recently, studies exploring mechanisms underlying PD progression have offered insights into multisystemic contributions to pathology, challenging the classic perspective of PD as a disease isolated to the brain. This shift in understanding has opened the door to potential new biomarkers from multiple sites in the body. This review focuses on emerging candidates for PD biomarkers in the context of current diagnostic approaches and multiple organ systems that contribute to disease.

scholarly journals Neuroregeneration in Parkinson’s Disease: From Proteins to Small Molecules

2019 ◽  
Vol 17 (3) ◽  
pp. 268-287 ◽  
Author(s):  
Yulia A. Sidorova ◽  
Konstantin P. Volcho ◽  
Nariman F. Salakhutdinov
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Small Molecules ◽  
Neurodegenerative Disorder ◽  
Dopamine Neurons ◽  
Current Therapy ◽  
Small Molecular Weight ◽  
Diagnostic Symptoms ◽  
Nigrostriatal Dopamine Neurons

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide, the lifetime risk of developing this disease is 1.5%. Motor diagnostic symptoms of PD are caused by degeneration of nigrostriatal dopamine neurons. There is no cure for PD and current therapy is limited to supportive care that partially alleviates disease signs and symptoms. As diagnostic symptoms of PD result from progressive degeneration of dopamine neurons, drugs restoring these neurons may significantly improve treatment of PD. </P><P> Method: A literature search was performed using the PubMed, Web of Science and Scopus databases to discuss the progress achieved in the development of neuroregenerative agents for PD. Papers published before early 2018 were taken into account. </P><P> Results: Here, we review several groups of potential agents capable of protecting and restoring dopamine neurons in cultures or animal models of PD including neurotrophic factors and small molecular weight compounds. </P><P> Conclusion: Despite the promising results of in vitro and in vivo experiments, none of the found agents have yet shown conclusive neurorestorative properties in PD patients. Meanwhile, a few promising biologicals and small molecules have been identified. Their further clinical development can eventually give rise to disease-modifying drugs for PD. Thus, intensive research in the field is justified.

scholarly journals Rotigotine patches (Neupro) in early Parkinson’s disease

2008 ◽  
Vol 9 (2) ◽  
pp. 115-119
Author(s):  
Viola Sacchi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Term Treatment ◽  
Symptomatic Therapy ◽  
Movement Initiation ◽  
Motor Disability ◽  
Postural Reflex ◽  
Alternative Approach ◽  
Long Term Treatment

Parkinson’s disease (PD) is a neurodegenerative disorder secondary to the progressive loss of dopaminergic neurons in the substantia nigra (a portion of the midbrain responsible for movement initiation and coordination) and appearance of bradykinesia, resting tremor, rigidity and postural reflex impairment. The most common symptomatic therapy is levodopa, a dopamine precursor; however, long-term treatment leads to involuntary movements and response fluctuations which add to the complexities of later disease-management. Monotherapy with dopamine agonists may represent an alternative approach with a reduced likelihood of motor complications; these drugs, initially introduced as adjunctive therapy to levodopa, are less effective in controlling motor disability and tend to cause more sideeffects than levodopa itself.

scholarly journals Ifenprodil Intracerebrally Offers Neuroprotection against 6-OHDA-Induced Toxicity in SD-Rats via Enhancing Autophagy Function

2021 ◽  
Author(s):  
Xinyu Zhao ◽  
Fugang Tian ◽  
Chunmin Guo ◽  
Xin Yu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuroprotective Effect ◽  
Beclin 1 ◽  
Dopamine Neurons ◽  
Intracerebral Injection ◽  
Glutamatergic Neurons ◽  
Neuron Damage ◽  
Pathogenic Change ◽  
Related Proteins

The progressive decline of dopamine neurons in the substantia nigra is the main pathogenic change in Parkinson's disease (PD). Studies have found that excessive excitement of glutamatergic neurons causes intracellular calcium overload and induces autophagy impairment, which is one of the main mechanisms of dopamine neuron damage. The neuroprotective effect of Ifenprodil against 6-OHDA-injured mice was studied in this study. Ifenprodil was administered intraperitoneally (i.p.) or intracerebrally to rats who had a nigral-striatum pathway lesioned by 6-OHDA stereotactic brain injection. The ability to move was evaluated. The survival of dopamine neurons in the nigral was determined using HE staining, while TH-positive expression was measured using immunohistochemistry. Western Blot was used to examine the expression of CaM protein and light chain 3 (LC3), Beclin-1, BNIP3LNix, and p62. The results revealed that Ifenprodil improves motor function in 6-OHDA rats, and intracerebral injection is more effective than systemic administration. The same results also found in HE and IHC. Ifenprodil enhanced LC3II, BNIP3LNix, and Beclin-1 while decreasing p62, p-CaMKII, and β-Ca expression. In addition, Ifenprodil reduced the activation of microglia caused by 6-OHDA. Overall, the findings imply that Ifenprodil intracerebrally may protect against Parkinson's disease via modulating autophagy-related proteins during 6-OHDA-induced toxicity.

scholarly journals Kajian potensi antioksidan dari tanaman herbal dan pengaruhnya terhadap penyakit Parkinson

2021 ◽  
Vol 17 (1) ◽  
pp. 80-95
Author(s):  
Indri Nuraeni Pratiwi ◽  
◽  
Widhya Aligita ◽  
Marita Kaniawati ◽  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Free Radicals ◽  
Neurodegenerative Disorder ◽  
Natural Antioxidants ◽  
Muscle Stiffness ◽  
Literature Study ◽  
Neuron Damage ◽  
Herbal Plants

Background: Parkinson's disease is the most common neurodegenerative disorder affecting more than 10 million people worldwide. This disease is characterized by progressive dopaminergic neuron damage in the substantia nigra. This damage can be triggered by aging and the presence of oxidative stress because of free radicals. Antioxidants can inhibit the formation of free radicals and reduce oxidative stress, so they can be used as an alternative treatment for Parkinson's disease. Objective: This review article aimed to provide information about the antioxidant effects of selected herbal plants on Parkinson's disease. Method: This study used literature study methods sourced from national and international scientific journals published in the last 5 years (2016-2020). Literature search were carried out using databases such as Google Scholar, PubMed®, ScienceDirect, and Garuda Portal. Results: The high content of antioxidants in plants could protect nerve cells from oxidative damage and reduce symptoms such as tremors, muscle stiffness, impaired coordination and motor balance in test animals. Conclusion: Natural antioxidants from herbal plants proved to be able to prevent oxidative stress caused by free radicals and reduce symptoms of Parkinson's disease. Keywords: Parkinson's disease, antioxidants, oxidative stress, herbal plants

scholarly journals The cell biology of Parkinson’s disease

2021 ◽  
Vol 220 (4) ◽  
Author(s):  
Nikhil Panicker ◽  
Preston Ge ◽  
Valina L. Dawson ◽  
Ted M. Dawson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Signaling Pathways ◽  
Cell Biology ◽  
Neurodegenerative Disorder ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Cellular Functions ◽  
Neuron Death ◽  
Associated Proteins

Parkinson’s disease (PD) is a progressive neurodegenerative disorder resulting from the death of dopamine neurons in the substantia nigra pars compacta. Our understanding of PD biology has been enriched by the identification of genes involved in its rare, inheritable forms, termed PARK genes. These genes encode proteins including α-syn, LRRK2, VPS35, parkin, PINK1, and DJ1, which can cause monogenetic PD when mutated. Investigating the cellular functions of these proteins has been instrumental in identifying signaling pathways that mediate pathology in PD and neuroprotective mechanisms active during homeostatic and pathological conditions. It is now evident that many PD-associated proteins perform multiple functions in PD-associated signaling pathways in neurons. Furthermore, several PARK proteins contribute to non–cell-autonomous mechanisms of neuron death, such as neuroinflammation. A comprehensive understanding of cell-autonomous and non–cell-autonomous pathways involved in PD is essential for developing therapeutics that may slow or halt its progression.

scholarly journals The Sources of Reactive Oxygen Species and Its Possible Role in the Pathogenesis of Parkinson’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Minrui Weng ◽  
Xiaoji Xie ◽  
Chao Liu ◽  
Kah-Leong Lim ◽  
Cheng-wu Zhang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neuron ◽  
Neurodegenerative Disorder ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Neuron Death ◽  
Neuron Damage

Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra. The precise mechanism underlying pathogenesis of PD is not fully understood, but it has been widely accepted that excessive reactive oxygen species (ROS) are the key mediator of PD pathogenesis. The causative factors of PD such as gene mutation, neuroinflammation, and iron accumulation all could induce ROS generation, and the later would mediate the dopaminergic neuron death by causing oxidation protein, lipids, and other macromolecules in the cells. Obviously, it is of mechanistic and therapeutic significance to understand where ROS are derived and how ROS induce dopaminergic neuron damage. In the present review, we try to summarize and discuss the main source of ROS in PD and the key pathways through which ROS mediate DA neuron death.

scholarly journals Effects of Oxidative Stress and Testosterone on Pro-Inflammatory Signaling in a Female Rat Dopaminergic Neuronal Cell Line

Endocrinology ◽  
2016 ◽  
Vol 157 (7) ◽  
pp. 2824-2835 ◽  
Author(s):  
Shaletha Holmes ◽  
Meharvan Singh ◽  
Chang Su ◽  
Rebecca L. Cunningham
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Androgen Receptor ◽  
Neurodegenerative Disorder ◽  
Dopamine Neurons ◽  
Female Rat ◽  
Stress Environment ◽  
Membrane Androgen Receptor

Parkinson's disease, a progressive neurodegenerative disorder, is associated with oxidative stress and neuroinflammation. These pathological markers can contribute to the loss of dopamine neurons in the midbrain. Interestingly, men have a 2-fold increased incidence for Parkinson's disease than women. Although the mechanisms underlying this sex difference remain elusive, we propose that the primary male sex hormone, testosterone, is involved. Our previous studies show that testosterone, through a putative membrane androgen receptor, can increase oxidative stress–induced neurotoxicity in dopamine neurons. Based on these results, this study examines the role of nuclear factor κ B (NF-κB), cyclooxygenase-2 (COX2), and apoptosis in the deleterious effects of androgens in an oxidative stress environment. We hypothesize, under oxidative stress environment, testosterone via a putative membrane androgen receptor will exacerbate oxidative stress–induced NF-κB/COX2 signaling in N27 dopaminergic neurons, leading to apoptosis. Our data show that testosterone increased the expression of COX2 and apoptosis in dopamine neurons. Inhibiting the NF-κB and COX2 pathway with CAPE and ibuprofen, respectively, blocked testosterone's negative effects on cell viability, indicating that NF-κB/COX2 cascade plays a role in the negative interaction between testosterone and oxidative stress on neuroinflammation. These data further support the role of testosterone mediating the loss of dopamine neurons under oxidative stress conditions, which may be a key mechanism contributing to the increased incidence of Parkinson's disease in men compared with women.

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