Parkinson’s disease: A current perspectives on Parkinson’s disease and key bioactive natural compounds as future potential drug candidates

2021 ◽  
Vol 22 ◽  
Author(s):  
Nabeel Ali ◽  
Amna Syeda ◽  
Tenzin Topgyal ◽  
Naseem Gaur ◽  
Asimul Islam
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Medicinal Plants ◽  
The Elderly ◽  
Natural Compounds ◽  
Muscle Stiffness ◽  
Drug Candidates ◽  
Gradual Loss ◽  
Life Threatening

: Parkinson’s disease (PD) is one of the most common types of neurological disorder prevailing worldwide and is rapidly increasing in the elderly population across the globe. The cause of PD is still unknown, but a number of genetic as well as environmental factors contributing to the pathogenesis of Parkinson’s disease have been identified. The hallmark of PD includes dopamine deficiency (neurotransmitter imbalance) due to the gradual loss of dopaminergic nerves in the substantia nigra in the midbrain. Studying the mutation of associated genes is particularly informative in understanding the fundamental molecular and pathogenic changes in PD. Intracellular accumulation of misfolded or degraded protein due to mutated gene leads to the manifestation of mitochondrial dysfunction, oxidative stress followed by multifaceted patho-physiologic symptoms. Other studies include the appearance of motor and non-motor responses like resting tremor, muscle stiffness, slow movement and anxiety, anaemia, constipation, rapid eye movement and sleep behaviour disorder. Many bioactive natural compounds have shown positive pharmacological results in treating a number of extensive disease models of PD. Despite the availability of an end number of potent medicinal plants around the world, limited research has been done associated with various neurological disorders, including PD. The currently available dopamine-based drug treatments have several side effects; further, they are not effective enough to combat PD completely. Therefore, various plant-based compounds with medicinal benefits have grabbed lots of attention from researchers to deal with various life-threatening neurodegenerative disorders like PD. On the basis of literature available to date, here, we have discussed and addressed the molecular basis, current scenario, and the best possible treatment of PD for the future with minimal or no side-effects using various key bioactive compounds from natural origin/medicinal plants.

scholarly journals Natural Compounds for the Management of Parkinson’s Disease and Attention-Deficit/Hyperactivity Disorder

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Juan Carlos Corona
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Attention Deficit Hyperactivity Disorder ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Attention Deficit ◽  
Neurological Disorders ◽  
Natural Compounds ◽  
Hyperactivity Disorder ◽  
Increased Risk

Parkinson’s disease (PD) is the second most common neurodegenerative disorder with an unknown aetiology. The pathogenic mechanisms include oxidative stress, mitochondrial dysfunction, protein dysfunction, inflammation, autophagy, apoptosis, and abnormal deposition of α-synuclein. Currently, the existing pharmacological treatments for PD cannot improve fundamentally the degenerative process of dopaminergic neurons and have numerous side effects. On the other hand, attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder of childhood and is characterised by hyperactivity, impulsivity, and inattention. The aetiology of ADHD remains unknown, although it has been suggested that its pathophysiology involves abnormalities in several brain regions, disturbances of the catecholaminergic pathway, and oxidative stress. Psychostimulants and nonpsychostimulants are the drugs prescribed for the treatment of ADHD; however, they have been associated with increased risk of substance use and have several side effects. Today, there are very few tools available to prevent or to counteract the progression of such neurological disorders. Thus, therapeutic approaches with high efficiency and fewer side effects are needed. This review presents a brief overview of the two neurological disorders and their current treatments, followed by a discussion of the natural compounds which have been studied as therapeutic agents and the mechanisms underlying the beneficial effects, in particular, the decrease in oxidative stress.

Parkinson's Disease: Long-Term Results of Levodopa Therapy

1982 ◽  
Vol 27 (4) ◽  
pp. 284-287 ◽  
Author(s):  
B. Pentland ◽  
D. Matthews ◽  
C. Mawdsley
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Levodopa Therapy ◽  
Long Term Results ◽  
Dopaminergic Therapy ◽  
Gradual Loss

The long-term results of levodopa therapy in Parkinsonian patients is described. Between January 1969 and December 1972, dopaminergic therapy was started in 186 patients with Parkinson's disease. Their progress after six months, five years and in the autumn of 1980, was assessed. The initial benefit in the majority of patients was followed by a gradual loss of efficacy in most patients with increasing side effects of central-mediated type. We suggest that it may be wise to delay the onset of levodopa therapy until progress of the disease makes treatment imperative.

Liposomes: Novel Drug Delivery Approach for Targeting Parkinson’s Disease

2020 ◽  
Vol 26 (37) ◽  
pp. 4721-4737 ◽  
Author(s):  
Bhumika Kumar ◽  
Mukesh Pandey ◽  
Faheem H. Pottoo ◽  
Faizana Fayaz ◽  
Anjali Sharma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Neural Cells ◽  
Blood Brain ◽  
The Brain

Parkinson’s disease is one of the most severe progressive neurodegenerative disorders, having a mortifying effect on the health of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out. This leads to symptoms like hypokinesia, rigidity, bradykinesia, and rest tremor. Parkinsonism cannot be cured, but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments, and physical therapies. Delivering drugs to the brain for treating Parkinson’s disease is very challenging. The blood-brain barrier acts as a highly selective semi-permeable barrier, which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson’s disease do not readily cross the blood barrier and further lead to several side-effects. Recent advancements in drug delivery technologies have facilitated drug delivery to the brain without flooding the bloodstream and by directly targeting the neurons. In the era of Nanotherapeutics, liposomes are an efficient drug delivery option for brain targeting. Liposomes facilitate the passage of drugs across the blood-brain barrier, enhances the efficacy of the drugs, and minimize the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targeting Parkinson’s disease.

scholarly journals Integrated network analysis identifying potential novel drug candidates and targets for Parkinson's disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pusheng Quan ◽  
Kai Wang ◽  
Shi Yan ◽  
Shirong Wen ◽  
Chengqun Wei ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Target ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Control Group ◽  
Drug Candidates ◽  
Novel Drug

AbstractThis study aimed to identify potential novel drug candidates and targets for Parkinson’s disease. First, 970 genes that have been reported to be related to PD were collected from five databases, and functional enrichment analysis of these genes was conducted to investigate their potential mechanisms. Then, we collected drugs and related targets from DrugBank, narrowed the list by proximity scores and Inverted Gene Set Enrichment analysis of drug targets, and identified potential drug candidates for PD treatment. Finally, we compared the expression distribution of the candidate drug-target genes between the PD group and the control group in the public dataset with the largest sample size (GSE99039) in Gene Expression Omnibus. Ten drugs with an FDR < 0.1 and their corresponding targets were identified. Some target genes of the ten drugs significantly overlapped with PD-related genes or already known therapeutic targets for PD. Nine differentially expressed drug-target genes with p < 0.05 were screened. This work will facilitate further research into the possible efficacy of new drugs for PD and will provide valuable clues for drug design.

scholarly journals Endoplasmic Reticulum Stress Regulators: New Drug Targets for Parkinson’s Disease

2021 ◽  
pp. 1-10
Author(s):  
Vera Kovaleva ◽  
Mart Saarma
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Er Stress ◽  
Protein Misfolding ◽  
Drug Targets ◽  
Dopamine Neurons ◽  
Drug Candidates ◽  
The Unfolded Protein Response

Parkinson’s disease (PD) pathology involves progressive degeneration and death of vulnerable dopamine neurons in the substantia nigra. Extensive axonal arborisation and distinct functions make this type of neurons particularly sensitive to homeostatic perturbations, such as protein misfolding and Ca2 + dysregulation. Endoplasmic reticulum (ER) is a cell compartment orchestrating protein synthesis and folding, as well as synthesis of lipids and maintenance of Ca2 +-homeostasis in eukaryotic cells. When misfolded proteins start to accumulate in ER lumen the unfolded protein response (UPR) is activated. UPR is an adaptive signalling machinery aimed at relieving of protein folding load in the ER. When UPR is chronic, it can either boost neurodegeneration and apoptosis or cause neuronal dysfunctions. We have recently discovered that mesencephalic astrocyte-derived neurotrophic factor (MANF) exerts its prosurvival action in dopamine neurons and in animal model of PD through the direct binding to UPR sensor inositol-requiring protein 1 alpha (IRE1α) and attenuation of UPR. In line with this, UPR targeting resulted in neuroprotection and neurorestoration in various preclinical PD animal models. Therefore, growth factors (GFs), possessing both neurorestorative activity and restoration of protein folding capacity are attractive as drug candidates for PD treatment especially their blood-brain barrier penetrating analogs and small molecule mimetics. In this review, we discuss ER stress as a therapeutic target to treat PD; we summarize the existing preclinical data on the regulation of ER stress for PD treatment. In addition, we point out the crucial aspects for successful clinical translation of UPR-regulating GFs and new prospective in GFs-based treatments of PD, focusing on ER stress regulation.

scholarly journals High-throughput behavioral screen in C. elegans reveals Parkinson’s disease drug candidates

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Salman Sohrabi ◽  
Danielle E. Mor ◽  
Rachel Kaletsky ◽  
William Keyes ◽  
Coleen T. Murphy
Keyword(s):  
Neural Network ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
High Throughput ◽  
Potential Candidate ◽  
Automated Scoring ◽  
C Elegans ◽  
Drug Candidates ◽  
Branched Chain ◽  
Approved Drugs

AbstractWe recently linked branched-chain amino acid transferase 1 (BCAT1) dysfunction with the movement disorder Parkinson’s disease (PD), and found that RNAi-mediated knockdown of neuronal bcat-1 in C. elegans causes abnormal spasm-like ‘curling’ behavior with age. Here we report the development of a machine learning-based workflow and its application to the discovery of potentially new therapeutics for PD. In addition to simplifying quantification and maintaining a low data overhead, our simple segment-train-quantify platform enables fully automated scoring of image stills upon training of a convolutional neural network. We have trained a highly reliable neural network for the detection and classification of worm postures in order to carry out high-throughput curling analysis without the need for user intervention or post-inspection. In a proof-of-concept screen of 50 FDA-approved drugs, enasidenib, ethosuximide, metformin, and nitisinone were identified as candidates for potential late-in-life intervention in PD. These findings point to the utility of our high-throughput platform for automated scoring of worm postures and in particular, the discovery of potential candidate treatments for PD.

scholarly journals Blood-brain barrier opening with focused ultrasound in Parkinson’s disease dementia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carmen Gasca-Salas ◽  
Beatriz Fernández-Rodríguez ◽  
José A. Pineda-Pardo ◽  
Rafael Rodríguez-Rojas ◽  
Ignacio Obeso ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Neurodegenerative Disorders ◽  
Focused Ultrasound ◽  
Temporal Cortex ◽  
Clinical State ◽  
Cognitive Improvement ◽  
Bbb Opening

AbstractMR-guided focused ultrasound (MRgFUS), in combination with intravenous microbubble administration, has been applied for focal temporary BBB opening in patients with neurodegenerative disorders and brain tumors. MRgFUS could become a therapeutic tool for drug delivery of putative neurorestorative therapies. Treatment for Parkinson’s disease with dementia (PDD) is an important unmet need. We initiated a prospective, single-arm, non-randomized, proof-of-concept, safety and feasibility phase I clinical trial (NCT03608553), which is still in progress. The primary outcomes of the study were to demonstrate the safety, feasibility and reversibility of BBB disruption in PDD, targeting the right parieto-occipito-temporal cortex where cortical pathology is foremost in this clinical state. Changes in β-amyloid burden, brain metabolism after treatments and neuropsychological assessments, were analyzed as exploratory measurements. Five patients were recruited from October 2018 until May 2019, and received two treatment sessions separated by 2–3 weeks. The results are set out in a descriptive manner. Overall, this procedure was feasible and reversible with no serious clinical or radiological side effects. We report BBB opening in the parieto-occipito-temporal junction in 8/10 treatments in 5 patients as demonstrated by gadolinium enhancement. In all cases the procedures were uneventful and no side effects were encountered associated with BBB opening. From pre- to post-treatment, mild cognitive improvement was observed, and no major changes were detected in amyloid or fluorodeoxyglucose PET. MRgFUS-BBB opening in PDD is thus safe, reversible, and can be performed repeatedly. This study provides encouragement for the concept of BBB opening for drug delivery to treat dementia in PD and other neurodegenerative disorders.

Dopamine agonists for parkinson’s disease

1991 ◽  
Vol 29 (2) ◽  
pp. 7-8
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Therapeutic Efficacy ◽  
Dopamine Agonists ◽  
Dopa Decarboxylase ◽  
Decarboxylase Inhibitor ◽  
Duration Of Action ◽  
Motor Disability ◽  
The Uk

Bromocriptine, lysuride (formerly lisuride, Revanil – Roche) and pergolide (not yet marketed in the UK) are dopamine agonists developed for use in the treatment of patients with Parkinson’s disease. Combination of a dopamine agonist with levodopa plus a dopa-decarboxylase inhibitor (‘co-dieldopa’)* may have advantages at all stages of the disease. The aim of combined co-dieldopa + agonist treatment is to limit some of the problems with prolonged co-dieldopa use alone; especially fluctuations in motor disability.1 It is still not clear how the three agonists compare with each other for therapeutic efficacy, duration of action, and side effects, nor how they are best combined with co-dieldopa.

Time Trends and Geographical Variation in Parkinson's Disease in Scotland

1992 ◽  
Vol 37 (4) ◽  
pp. 112-115 ◽  
Author(s):  
W.C.S. Smith ◽  
W.J. Mutch
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Time Trends ◽  
Geographical Variation ◽  
The Elderly ◽  
Epidemiological Studies ◽  
Space Distribution ◽  
Mortality Data ◽  
Time And Space ◽  
Factors Affecting

Parkinson's disease is a common and disabling condition which principally affects the elderly. The time and space distribution of Parkinson's disease has been examined to determine if it provides clues as to aetiology and factors affecting its distribution. Previous studies have used mortality data,1 data from epidemiological studies,2 and pre scribing information particularly with regard to the use of levodopa.3 These studies have looked within countries and between countries.

Sign in / Sign up

Export Citation Format

Share Document