scholarly journals CRITICAL REVIEW OF PHARMACOGENOMICS IN ANTIPARKINSONIAN DRUG THERAPY: IMPACT ON CLINICAL MANAGEMENT OF PARKINSON’S DISEASE

2016 ◽  
Vol 9 (6) ◽  
pp. 24
Author(s):  
Poornima R ◽  
Sabreen Bashir
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Critical Review ◽  
Neurodegenerative Disorder ◽  
Future Research ◽  
Comt Inhibitors ◽  
Gait Dysfunction ◽  
Non Motor Symptoms ◽  
Antiparkinsonian Drugs

Parkinson’s disease is a progressive neurodegenerative disorder characterized by rest tremors, bradykinesia , rigidity , postural instability , gait dysfunction and several non motor symptoms . The marked difference in drug response and adverse effect profile among patients led to search of genetic markers and polymorphism associated with response to antiparkinsonian drugs which will enable us to predict an individuals   response to drugs in terms of both efficacy and toxicity. Hence efforts to define the role of genetic polymorphism in optimizing pharmacotherapy of Parkinson’s disease have been undertaken and some promising genetic loci for the treatment have been determined. Therefore we aim to present a critical review of  pharmacogenetic aspects of levodopa ,  dopamine agonists and COMT inhibitors and describe gene polymorphism of interest for future research. 

Peripheral Immunity, Immunoaging and Neuroinflammation in Parkinson’s Disease

2019 ◽  
Vol 26 (20) ◽  
pp. 3719-3753 ◽  
Author(s):  
Natasa Kustrimovic ◽  
Franca Marino ◽  
Marco Cosentino
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Immune System ◽  
Neurodegenerative Disorder ◽  
Neurodegenerative Process ◽  
Progressive Degeneration ◽  
Cytokine Levels ◽  
Inflammatory Phenotype ◽  
Immune Challenges

:Parkinson’s disease (PD) is the second most common neurodegenerative disorder among elderly population, characterized by the progressive degeneration of dopaminergic neurons in the midbrain. To date, exact cause remains unknown and the mechanism of neurons death uncertain. It is typically considered as a disease of central nervous system (CNS). Nevertheless, numerous evidence has been accumulated in several past years testifying undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is mainly associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. Nevertheless, active participation of immune system as well has been noted, such as, elevated levels of cytokine levels in blood, the presence of auto antibodies, and the infiltration of T cell in CNS. Moreover, infiltration and reactivation of those T cells could exacerbate neuroinflammation to greater neurotoxic levels. Hence, peripheral inflammation is able to prime microglia into pro-inflammatory phenotype, which can trigger stronger response in CNS further perpetuating the on-going neurodegenerative process.:In the present review, the interplay between neuroinflammation and the peripheral immune response in the pathobiology of PD will be discussed. First of all, an overview of regulation of microglial activation and neuroinflammation is summarized and discussed. Afterwards, we try to collectively analyze changes that occurs in peripheral immune system of PD patients, suggesting that these peripheral immune challenges can exacerbate the process of neuroinflammation and hence the symptoms of the disease. In the end, we summarize some of proposed immunotherapies for treatment of PD.

scholarly journals Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiao-yi Kuai ◽  
Xiao-han Yao ◽  
Li-juan Xu ◽  
Yu-qing Zhou ◽  
Li-ping Zhang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Motor Symptoms ◽  
Gastrointestinal Dysfunction ◽  
Before And After ◽  
Non Motor Symptoms

AbstractParkinson’s disease (PD) is a neurodegenerative disorder and 70–80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.

scholarly journals Redefining the strategy for the use of COMT inhibitors in Parkinson’s disease: the role of opicapone

2021 ◽  
pp. 1-15
Author(s):  
Peter Jenner ◽  
José-Francisco Rocha ◽  
Joaquim J Ferreira ◽  
Olivier Rascol ◽  
Patrício Soares-da-Silva
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Comt Inhibitors

Parkinson's Disease Genetics and Pathophysiology

2021 ◽  
Vol 44 (1) ◽  
pp. 87-108
Author(s):  
Gabriel E. Vázquez-Vélez ◽  
Huda Y. Zoghbi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Variants ◽  
Neurodegenerative Disorder ◽  
Disease Risk ◽  
Lewy Bodies ◽  
Substantia Nigra Pars Compacta ◽  
Disease Modifying ◽  
Common Neurodegenerative Disorder

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by degeneration of the substantia nigra pars compacta and by accumulation of α-synuclein in Lewy bodies. PD is caused by a combination of environmental factors and genetic variants. These variants range from highly penetrant Mendelian alleles to alleles that only modestly increase disease risk. Here, we review what is known about the genetics of PD. We also describe how PD genetics have solidified the role of endosomal, lysosomal, and mitochondrial dysfunction in PD pathophysiology. Finally, we highlight how all three pathways are affected by α-synuclein and how this knowledge may be harnessed for the development of disease-modifying therapeutics.

scholarly journals Swallowing dysfunctions in Parkinson’s disease patients: a novel challenge for the internist

2019 ◽  
Vol 13 (2) ◽  
pp. 91-94 ◽  
Author(s):  
Elena Barbagelata ◽  
Antonello Nicolini ◽  
Paola Tognetti
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Practice ◽  
Aspiration Pneumonia ◽  
Neurodegenerative Disorder ◽  
Movement Pattern ◽  
Morbidity And Mortality ◽  
Motor Symptoms ◽  
Common Causes ◽  
Non Motor Symptoms

Parkinson’s disease (PD) is a chronic neurodegenerative disorder with a typical movement pattern, as well as different, less studied non-motor symptoms such as dysphagia. Disease-related disorders in efficacy or safety in the process of swallowing usually lead to malnutrition, dehydration or pneumonia. Dysphagia and subsequent aspiration pneumonia are common causes of morbidity and mortality in those with PD. The aim of this review is to identify and evaluate the existing literature on swallowing disorders in PD and providing recommendations for clinical practice routine.

scholarly journals Molecular evolutionary and structural analysis of human UCHL1 gene demonstrates the relevant role of intragenic epistasis in Parkinson’s disease and other neurological disorders

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Muhammad Saqib Nawaz ◽  
Razia Asghar ◽  
Nashaiman Pervaiz ◽  
Shahid Ali ◽  
Irfan Hussain ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Structural Analysis ◽  
Neurodegenerative Disorder ◽  
Soluble Form ◽  
Evolutionary Pattern ◽  
Protein Segment ◽  
Interaction Sites ◽  
Relevant Role

Abstract Background Parkinson’s disease (PD) is the second most common neurodegenerative disorder. PD associated human UCHL1 (Ubiquitin C-terminal hydrolase L1) gene belongs to the family of deubiquitinases and is known to be highly expressed in neurons (1–2% in soluble form). Several functions of UCHL1 have been proposed including ubiquitin hydrolyze activity, ubiquitin ligase activity and stabilization of the mono-ubiquitin. Mutations in human UCHL1 gene have been associated with PD and other neurodegenerative disorders. The present study aims to decipher the sequence evolutionary pattern and structural dynamics of UCHL1. Furthermore, structural and interactional analysis of UCHL1 was performed to help elucidate the pathogenesis of PD. Results The phylogenetic tree topology suggests that the UCHL1 gene had originated in early gnathostome evolutionary history. Evolutionary rate analysis of orthologous sequences reveals strong purifying selection on UCHL1. Comparative structural analysis of UCHL1 pinpoints an important protein segment spanning amino acid residues 32 to 39 within secretion site with crucial implications in evolution and PD pathogenesis through a well known phenomenon called intragenic epistasis. Identified critical protein segment appears to play an indispensable role in protein stability, proper protein conformation as well as harboring critical interaction sites. Conclusions Conclusively, the critical protein segment of UCHL1 identified in the present study not only demonstrates the relevant role of intraprotein conformational epistasis in the pathophysiology of PD but also offers a novel therapeutic target for the disease.

Impulse-Control Disorders in Parkinson's Disease

CNS Spectrums ◽  
2008 ◽  
Vol 13 (8) ◽  
pp. 690-698 ◽  
Author(s):  
Joseph M. Ferrara ◽  
Mark Stacy
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Replacement Therapy ◽  
Impulse Control ◽  
Neurodegenerative Disorder ◽  
Psychosocial Impairment ◽  
Olfactory Loss ◽  
Dopamine Replacement Therapy ◽  
Compulsive Behaviors ◽  
Non Motor Symptoms

ABSTRACTParkinson's disease is a neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, and resting tremor. Increasingly, Parkinson's disease has been associated with a broad spectrum of non-motor symptoms, such as olfactory loss, sleep disorders, autonomic dysfunction, cognitive impairment, psychosis, depression, anxiety, and apathy. In addition, a minority of Parkinson's disease patients develop compulsive behaviors while receiving dopamine-replacement therapy, including medication hoarding, pathological gambling, binge eating, hyperlibidinous behavior, compulsive shopping, and punding. These behaviors may result in psychosocial impairment for patients and therapeutic challenges for clinicians. This article reviews the anatomic substrates, behavioral spectrum, associated factors, and potential treatments for dopamine-replacement therapy-related compulsions in Parkinson's disease.

scholarly journals Chaperone-Mediated Autophagy and Mitochondrial Homeostasis in Parkinson’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-7
Author(s):  
Ruixin Yang ◽  
Guodong Gao ◽  
Zixu Mao ◽  
Qian Yang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Lewy Bodies ◽  
Substantia Nigra Pars Compacta ◽  
Mitochondrial Homeostasis ◽  
New Findings ◽  
Novel Therapeutic Strategies ◽  
Chaperone Mediated Autophagy

Parkinson’s disease (PD), a complex neurodegenerative disorder, is pathologically characterized by the formation of Lewy bodies and loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Mitochondrial dysfunction is considered to be one of the most important causative mechanisms. In addition, dysfunction of chaperone-mediated autophagy (CMA), one of the lysosomal proteolytic pathways, has been shown to play an important role in the pathogenesis of PD. An exciting and important development is recent finding that CMA and mitochondrial quality control may be linked. This review summarizes the studies revealing the link between autophagy and mitochondrial function. Discussions are focused on the connections between CMA and mitochondrial failure and on the role of MEF2D, a neuronal survival factor, in mediating the regulation of mitochondria in the context of CMA. These new findings highlight the need to further explore the possibility of targeting the MEF2D-mitochondria-CMA network in both understanding the PD pathogenesis and developing novel therapeutic strategies.

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