Selected natural and synthetic agents effective against Parkinson’s disease with diverse mechanisms

2021 ◽  
Vol 21 ◽  
Author(s):  
Hayrettin Ozan Gulcan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Dopamine Metabolism ◽  
Dopaminergic Agonists ◽  
Alternative Drug ◽  
Synthetic Agents ◽  
Disease Modifying

: Similar to other neurodegenerative diseases, Parkinson’s disease (PD) has been extensively investigated with respect to its neuropathological background and possible treatment options. Since the symptomatic outcomes are generally related to dopamine deficiency, the current treatment strategies towards PD mainly employ dopaminergic agonists as well as the compounds acting on dopamine metabolism. These drugs do not provide disease modifying properties; therefore alternative drug discovery studies focus on targets involved in the progressive neurodegenerative character of PD. This study has aimed to present the pathophysiology of PD concomitant to the representation of drugs and promising molecules displaying activity against the validated and non-validated targets of PD.

scholarly journals Neuropsychiatric symptoms in Parkinson's disease: aetiology, diagnosis and treatment

2020 ◽  
Vol 26 (6) ◽  
pp. 333-342 ◽  
Author(s):  
Shoned Jones ◽  
Kelli M. Torsney ◽  
Lily Scourfield ◽  
Katie Berryman ◽  
Emily J. Henderson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuropsychiatric Symptoms ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Motor Disorder ◽  
Dopamine Dysregulation Syndrome ◽  
Disease Aetiology ◽  
Neuropsychiatric Manifestations ◽  
Assessment Scales

SUMMARYHistorically, Parkinson's disease was viewed as a motor disorder and it is only in recent years that the spectrum of non-motor disorders associated with the condition has been fully recognised. There is a broad scope of neuropsychiatric manifestations, including depression, anxiety, apathy, psychosis and cognitive impairment. Patients are more predisposed to delirium, and Parkinson's disease treatments give rise to specific syndromes, including impulse control disorders, dopamine agonist withdrawal syndrome and dopamine dysregulation syndrome. This article gives a broad overview of the spectrum of these conditions, describes the association with severity of Parkinson's disease and the degree to which dopaminergic degeneration and/or treatment influence symptoms. We highlight useful assessment scales that inform diagnosis and current treatment strategies to ameliorate these troublesome symptoms, which frequently negatively affect quality of life.

scholarly journals Emerging regenerative medicine and tissue engineering strategies for Parkinson’s disease

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
James P. Harris ◽  
Justin C. Burrell ◽  
Laura A. Struzyna ◽  
H. Isaac Chen ◽  
Mijail D. Serruya ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Regenerative Medicine ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Substantia Nigra Pars Compacta ◽  
Patient Specific ◽  
Motor Deficits ◽  
Nigrostriatal Pathway ◽  
Future Challenges

AbstractParkinson’s disease (PD) is the second most common progressive neurodegenerative disease, affecting 1–2% of people over 65. The classic motor symptoms of PD result from selective degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in a loss of their long axonal projections to the striatum. Current treatment strategies such as dopamine replacement and deep brain stimulation (DBS) can only minimize the symptoms of nigrostriatal degeneration, not directly replace the lost pathway. Regenerative medicine-based solutions are being aggressively pursued with the goal of restoring dopamine levels in the striatum, with several emerging techniques attempting to reconstruct the entire nigrostriatal pathway—a key goal to recreate feedback pathways to ensure proper dopamine regulation. Although many pharmacological, genetic, and optogenetic treatments are being developed, this article focuses on the evolution of transplant therapies for the treatment of PD, including fetal grafts, cell-based implants, and more recent tissue-engineered constructs. Attention is given to cell/tissue sources, efficacy to date, and future challenges that must be overcome to enable robust translation into clinical use. Emerging regenerative medicine therapies are being developed using neurons derived from autologous stem cells, enabling the construction of patient-specific constructs tailored to their particular extent of degeneration. In the upcoming era of restorative neurosurgery, such constructs may directly replace SNpc neurons, restore axon-based dopaminergic inputs to the striatum, and ameliorate motor deficits. These solutions may provide a transformative and scalable solution to permanently replace lost neuroanatomy and improve the lives of millions of people afflicted by PD.

scholarly journals Assessment of therapeutic strategies for management of impulse control disorder in Parkinson’s disease

2021 ◽  
Vol 79 (11) ◽  
pp. 989-994
Author(s):  
Mayela Rodríguez-Violante ◽  
Yazmín Ríos-Solís ◽  
Oscar Esquivel-Zapata ◽  
Fanny Herrera ◽  
Susana López-Alamillo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Impulse Control ◽  
Real Life ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Real Life Setting ◽  
Frequency Of Use ◽  
Baseline Evaluation

ABSTRACT Background: Impulse control disorders (ICD) occur frequently in individuals with Parkinson's disease. So far, prevention is the best treatment. Several strategies for its treatment have been suggested, but their frequency of use and benefit have scarcely been explored. Objective: To investigate which strategy is the most commonly used in a real-life setting and its rate of response. Methods: A longitudinal study was conducted. At the baseline evaluation, data on current treatment and ICD status according to QUIP-RS were collected. The treatment strategies were categorized as “no-change”, dopamine agonist (DA) dose lowering, DA removal, DA switch or add-on therapy. At the six-month follow-up visit, the same tools were applied. Results: A total of 132 individuals (58.3% men) were included; 18.2% had at least one ICD at baseline. The therapeutic strategy most used in the ICD group was no-change (37.5%), followed by DA removal (16.7%), DA switch (12.5%) and DA lowering (8.3%). Unexpectedly, in 20.8% of the ICD subjects the DA dose was increased. Overall, nearly 80% of the subjects showed remission of their ICD at follow-up. Conclusions: Regardless of the therapy used, most of the subjects presented remission of their ICD at follow-up Further research with a longer follow-up in a larger sample, with assessment of decision-making processes, is required in order to better understand the efficacy of strategies for ICD treatment.

Understanding the Pathogenesis Involved in Parkinson’s Disease and Potential Therapeutic Treatment Strategies

2020 ◽  
Vol 20 (2) ◽  
pp. 88-102
Author(s):  
Meenakshi Dhanawat ◽  
Dinesh K. Mehta ◽  
Sumeet Gupta ◽  
Rina Das
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuronal Degeneration ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Lewy Bodies ◽  
Symptomatic Treatment ◽  
Point Of Interest ◽  
Prophylactic Measures ◽  
Drug Regimens

: A vast advancement has been made in the treatment related to central nervous system disorders especially Parkinson’s disease. The development in therapeutics and a better understanding of the targets results in upsurge of many promising therapies for Parkinson’s disease. Parkinson’s disease is defined by neuronal degeneration and neuroinflammation and it is reported that the presence of the neurofibrillary aggregates such as Lewy bodies is considered as the marker. Along with this, it is also characterized by the presence of motor and non-motor symptoms, as seen in Parkinsonian patients. A lot of treatment options mainly focus on prophylactic measures or the symptomatic treatment of Parkinson’s disease. : Neuroinflammation and neurodegeneration are the point of interest which can be exploited as a new target to emphasis on Parkinson’s disease. : A thorough study of these targets helps in modifications of those molecules which are particularly involved in causing the neuronal degeneration and neuroinflammation in Parkinson’s disease. : A lot of drug regimens are available for the treatment of Parkinson’s disease, although levodopa remains the choice of drug for controlling the symptoms, yet is accompanied with significant snags. It is always suggested to use other drug therapies concomitantly with levodopa. : A number of significant causes and therapeutic targets for Parkinson’s disease have been identified in the last decade, here an attempt was made to highlight the most significant of them. It was also found that the treatment regimen and involvement of therapies are totally dependent on individuals and can be tailored to the needs of each individual patient.

scholarly journals Bright Light Therapy in Parkinson's Disease: An Overview of the Background and Evidence

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Sonja Rutten ◽  
Chris Vriend ◽  
Odile A. van den Heuvel ◽  
Jan H. Smit ◽  
Henk W. Berendse ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Circadian Rhythm ◽  
Sleep Disorders ◽  
Treatment Options ◽  
Bright Light ◽  
Light Therapy ◽  
Current Treatment ◽  
Bright Light Therapy ◽  
Positive Effect

Sleep disorders are common in Parkinson's disease (PD) and seem to be strongly associated with depression. It has been suggested that sleep disorders as well as depression are caused by a disturbed circadian rhythm. Indeed, PD patients are prone to misalignment of their circadian rhythm due to various factors, and many patients with PD display a phase advance of their circadian rhythm. Current treatment options for sleep disorders and depression in patients with PD are limited and can have serious side effects; alternative treatments are therefore badly needed. Bright light therapy (BLT) restores circadian rhythmicity effectively in mood- and sleep-disturbed patients without PD. The few studies that focused on the efficacy of BLT in patients with PD demonstrated a positive effect of BLT not only on sleep and mood but also on motor function. More research on the neurobiology and efficacy of BLT in PD is warranted.

scholarly journals Genetic Basis and Novel Treatment Strategies in Parkinson's Disease – A Review

2021 ◽  
Vol 5 (1) ◽  
pp. 1-5
Author(s):  
Nagare Santosh Gangadhar ◽  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Metal Ion ◽  
Genetic Basis ◽  
Neurodegenerative Disorder ◽  
Symptomatic Relief ◽  
Ion Homeostasis ◽  
Treatment Strategies ◽  
Metal Ion Homeostasis ◽  
Disease Modifying

Parkinson's disease (PD) is the 2nd most common progressive neurodegenerative disorder after Alzheimer's disease. Approximately 60000 are diagnosed with Parkinson's disease each year and more than 10 million people are living with PD. PD is a neurodegenerative disorder in addition to the causes of PD are so many, it's not caused by a single pathophysiologic disturbance. So many drugs are available to treat PD but all are only for symptomatic relief no one drug is a disease-modifying agent. Although so many targets are available for targeting the Synuclein alpha, mitochondrial oxidative stress, autophagy, targeting glial cell inflammation, targeting metal ion homeostasis. But till now no one drug is successful in targeting these targets. In this review, we have summarized the genetic basis and novel targets available for the disease-modifying strategy for PD.

scholarly journals The Future of Targeted Gene-Based Treatment Strategies and Biomarkers in Parkinson’s Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 912 ◽  
Author(s):  
Alexia Polissidis ◽  
Lilian Petropoulou-Vathi ◽  
Modestos Nakos-Bimpos ◽  
Hardy J. Rideout
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Treatment Strategies ◽  
Disease Diagnosis ◽  
Alpha Synuclein ◽  
Strategy Development ◽  
Early Detection Of Disease ◽  
Medical Needs ◽  
Disease Modifying Therapies ◽  
Disease Modifying

Biomarkers and disease-modifying therapies are both urgent unmet medical needs in the treatment of Parkinson’s disease (PD) and must be developed concurrently because of their interdependent relationship: biomarkers for the early detection of disease (i.e., prior to overt neurodegeneration) are necessary in order for patients to receive maximal therapeutic benefit and vice versa; disease-modifying therapies must become available for patients whose potential for disease diagnosis and prognosis can be predicted with biomarkers. This review provides an overview of the milestones achieved to date in the therapeutic strategy development of disease-modifying therapies and biomarkers for PD, with a focus on the most common and advanced genetically linked targets alpha-synuclein (SNCA), leucine-rich repeat kinase-2 (LRRK2) and glucocerebrosidase (GBA1). Furthermore, we discuss the convergence of the different pathways and the importance of patient stratification and how these advances may apply more broadly to idiopathic PD. The heterogeneity of PD poses a challenge for therapeutic and biomarker development, however, the one gene- one target approach has brought us closer than ever before to an unprecedented number of clinical trials and biomarker advancements.

Psychosis in Parkinson’s Disease: Current Treatment Options and Impact on Patients and Caregivers

2021 ◽  
Vol 34 (4) ◽  
pp. 274-279
Author(s):  
Gilad S. Segal ◽  
Sophie J. Xie ◽  
Saif-ur-Rahman Paracha ◽  
George T. Grossberg
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Atypical Antipsychotics ◽  
Treatment Options ◽  
Current Treatment ◽  
Visual Hallucinations ◽  
Mesolimbic Pathway ◽  
Sequential Development ◽  
Home Placement

Parkinson’s disease (PD) is the second most common neurodegenerative disease seen in older adults after Alzheimer’s disease, with increasing prevalence worldwide. Parkinson’s disease psychosis (PDP) is a common, non-motor feature of PD, which increases caregiver stress and is a risk-factor for nursing home placement. In this paper we review PDP epidemiology, features, diagnosis, and treatment. PDP most often presents with sequential development of minor and then increasingly complex visual hallucinations mediated by dopaminergic-serotonergic interactions activating the mesolimbic pathway, with contributions from other structures and neurotransmitters. Appropriate evaluation of differential diagnoses for psychosis is vital before diagnosing PDP. Initial treatment should involve non-pharmacologic approaches. If these are unsuccessful and PDP symptoms significantly impact the patient’s and or their caregivers’ quality of life and functions, then pharmacotherapy is indicated. Pimavanserin is a recently FDA-approved pharmacologic treatment for PDP with a better profile of balanced effectiveness and safety compared to previous use of atypical antipsychotics. Early diagnosis and safer, more effective treatments for PDP should help reduce caregiver burden and enable caregivers to continue to provide care at home versus institutionalization.

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