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 An optimized RNN-LSTM approach for parkinson’s disease early detection using speech features

2021 ◽  
Vol 10 (5) ◽  
pp. 2503-2512
Author(s):  
Hadeel Ahmed Abd El Aal ◽  
Shereen A. Taie ◽  
Nashwa El-Bendary
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Detection ◽  
Short Term Memory ◽  
Neurodegenerative Disorder ◽  
Classification Performance ◽  
The Body ◽  
Testing Dataset ◽  
Benchmark Datasets ◽  
Speech Features

Parkinson's disease (PD) is the second most common neurodegenerative disorder disease right after Alzheimer's and the most common movement disorder for elderly people. It is characterized as a progressive loss of muscle control, which leads to trembling characterized by uncontrollable shaking, or (tremors) in different parts of the body. In recent years, deep learning (DL) models achieved significant progress in automatic speech recognition, however, limited studies addressed the problem of distinguishing people with PD for further clinical diagnosis. In this paper, an approach for the early detection of patients with PD using speech features was proposed, a recurrent neural network (RNN) with long short-term memory (LSTM) is applied with the batch normalization layer and adaptive moment estimation (ADAM) optimization algorithm used after the network hidden layers to improve the classification performance. The proposed approach is applied with 2 benchmark datasets of speech features for patients with PD and healthy control subjects. The proposed approach achieved an accuracy of 95.8% and MCC=92.04% for the testing dataset. In future work, we aim to increase the voice features that will be worked on and consider using handwriting kinematic features.

Orally Administered Nanotherapeutics For Parkinson’s Disease: An Old Delivery System Yet More Acceptable

2020 ◽  
Vol 26 (19) ◽  
pp. 2280-2290 ◽  
Author(s):  
Nidhi Aggarwal ◽  
Zufika Qamar ◽  
Saleha Rehman ◽  
Sanjula Baboota ◽  
Javed Ali
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Drug Delivery Systems ◽  
Neurodegenerative Disorder ◽  
Intestinal Barrier ◽  
Oral Route ◽  
Delivery Systems ◽  
The Body ◽  
Area Of Interest

As per the present global scenario, Parkinson’s disease (PD) is considered to be the second most common neurodegenerative disorder which is a keen area of interest among researchers. The conventional therapies generally employed against PD are associated with serious drawbacks including limited transport across selectively permeable BBB, hepatic metabolism, intestinal barrier, etc. This urges the need to develop novel therapeutic alternatives. The oral route being the most preferred route of administration needs to be explored for new and more intelligent drug delivery systems. Nanotechnology has been proposed to play a promising role in reversing the progression of the disease via the oral route. Nanocarriers, namely nanoparticles, lipid nanoparticles, nanoemulsions, nanocrystals, nanomicellar formulations, self-nanoemulsifying drug delivery systems and alginate nanocomposites have been investigated upon to modulate the fate of drugs inside the human body when administered orally. The development of various nanotherapeutics for the treatment of PD has been reviewed, depicting an enhanced bioavailability to provide a desired therapeutic outcome. The new advances in the therapy have been explored and highlighted through the body of this review. However, a therapeutically effective concentration at the target site remains a challenge, therefore extensive exploration in the field of nanotherapeutics may facilitate superior drug delivery to CNS via oral route thereby improving the state of disease progression.

scholarly journals Spinal Anesthesia for Laparoscopic Cholecystectomy in Parkinson’s disease

2018 ◽  
Vol 56 (211) ◽  
pp. 701-704
Author(s):  
Binod Gautam ◽  
Bikash Baral
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Laparoscopic Cholecystectomy ◽  
General Anaesthesia ◽  
Spinal Anaesthesia ◽  
Neurodegenerative Disorder ◽  
Abdominal Pressure ◽  
Muscle Rigidity ◽  
Sensory Blockade ◽  
Organ Systems

Parkinson’s disease, a neurodegenerative disorder, presents with resting tremor, muscle rigidity and bradykinesia. Affecting multiple organ-systems, it’s an important cause of peri-operative morbidity. General anaesthesia may deteriorate cardio-pulmonary and neuro-cognitive functions; moreover, medications used may interact with anti-parkinsonian agents. Spinal anaesthesia is usually avoided in Parkinson’s disease. However, it offers neurologic monitoring and less surgical stress response and avoids complications of general anaesthesia. This case report aims to demonstrate application of spinal anaesthesia for laparoscopic cholecystectomy in a Parkinson’s elderly with pulmonary dysfunction and anticipated difficult airway management. Sensory blockade of third thoracic dermatome was achieved. Bupivacaine was instilled intra-peritoneally. Surgery was smooth at low intra-abdominal pressure. Regular Paracetamol provided satisfactory post-operative analgesia. Single episode of post-operative vomiting was effectively managed. Without deterioration, patient was discharged from hospital on third day. Spinal anaesthesia is a valid technique for laparoscopic cholecystectomy in needy patients with multiple peri-operative risks.

scholarly journals Dietary Antioxidants and Parkinson’s Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 570 ◽  
Author(s):  
Han-A Park ◽  
Amy C. Ellis
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Redox Homeostasis ◽  
The United States ◽  
Lifestyle Changes ◽  
Antioxidant Defenses ◽  
Dietary Antioxidants

Parkinson’s disease (PD) is a neurodegenerative disorder caused by the depletion of dopaminergic neurons in the basal ganglia, the movement center of the brain. Approximately 60,000 people are diagnosed with PD in the United States each year. Although the direct cause of PD can vary, accumulation of oxidative stress-induced neuronal damage due to increased production of reactive oxygen species (ROS) or impaired intracellular antioxidant defenses invariably occurs at the cellular levels. Pharmaceuticals such as dopaminergic prodrugs and agonists can alleviate some of the symptoms of PD. Currently, however, there is no treatment to halt the progression of PD pathology. Due to the nature of PD, a long and progressive neurodegenerative process, strategies to prevent or delay PD pathology may be well suited to lifestyle changes like dietary modification with antioxidant-rich foods to improve intracellular redox homeostasis. In this review, we discuss cellular and genetic factors that increase oxidative stress in PD. We also discuss neuroprotective roles of dietary antioxidants including vitamin C, vitamin E, carotenoids, selenium, and polyphenols along with their potential mechanisms to alleviate PD pathology.

scholarly journals Baicalein Mediates Mitochondrial Autophagy via miR-30b and the NIX/BNIP3 Signaling Pathway in Parkinson’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Min Chen ◽  
Li Peng ◽  
Ping Gong ◽  
Xiaoli Zheng ◽  
Tao Sun ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Membrane Potential ◽  
Mitochondrial Membrane ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Protein Levels ◽  
Neurological Score ◽  
6 Hydroxydopamine ◽  
Related Proteins

Parkinson’s disease (PD) is regarded as a severe neurodegenerative disorder. Baicalein is involved in the treatment of PD. This study explored the mechanism of baicalein in PD. The PD rat model was established using 6-hydroxydopamine. The neurologic score, dopamine (DA) content, apoptotic cells, and neuronal damage were evaluated after rats were treated with baicalein. Autophagy in PD rats was inhibited using 3-methyladenine (3-MA). The mitochondrial membrane potential (MMP) and autophagy-related proteins (LC3, P62) were detected. Next, agomiR-30b was transfected into PD rats. The targeting relation between miR-30b and NIX was predicted and verified. Then, sh-NIX was transfected into PD rats, and the effects of miR-30b and NIX on MMP, LC3, and P62 were assessed. When miR-30b was overexpressed using agomiR-30b, the NIX and BNIP3 levels were detected. Baicalein increased the neurological score and restored DA content, neurons, MMP, and mitochondrial autophagy protein levels. Baicalein inhibited miR-30b expression and miR-30b targeted NIX. miR-30b upregulation or NIX silencing reversed the effect of baicalein on MMP and mitochondrial autophagy. Baicalein upregulated NIX and BNIP3 expressions, while miR-30b overexpression inhibited NIX and BNIP3 expressions. In summary, baicalein mediated mitochondrial autophagy and restored neuronal activity by downregulating miR-30b and activating the NIX/BNIP3 pathway, thus protecting against PD.

scholarly journals Management of Symptoms of Parkinsonism Through Panchakarma Therapy

2020 ◽  
Author(s):  
Ashok Kumar Pandey ◽  
Saurabh Mishra ◽  
Alka Mishra
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Herbal Medicines ◽  
The Elderly ◽  
The Body ◽  
Lower Back ◽  
Patient Reported ◽  
The Brain

Background: Parkinson's disease is a disabling neurodegenerative disorder, mainly affecting the elderly population. Symptoms of Parkinsonism include motor function abnormalities, tremors in hands and legs, postural instability, etc. Side-effect free, long-term management of Parkinsonism is still a challenge. According to Ayurveda, the disease that resembles the symptoms associated with Parkinson's disease is Kampavata (kampa means tremors), which is primarily caused by the imbalance of the Vata Dosha. Various Panchakarma procedures have been found useful in the treatment of different Vata Vyadhis (diseases caused by the imbalance of Vata Dosha).Methodology: Panchakarma therapy was administered for 19 days to a male patient suffering from symptoms of Parkinsonism (Kampavata) since about nine months, as well as other associated ailments. According to Ayurveda, Kampavata is primarily associated with Vata imbalance. Hence, Vata pacifying herbal medicines, that also provide strengthening and nourishing effect to the degenerative tissues of the body, as well as nourishment to the brain, were used.Results: The patient experienced significant relief in the tremors in B/L hands, numbness in B/L big toes, weakness in lower extremity, and lower back pain. The patient also experienced notable relief in the complaints of Constipation, Gastric upset, and Flatus. Overall, the patient reported a satisfactory experience after taking the therapy.Conclusion: Panchakarma therapy showed encouraging results in the management of symptoms associated with Parkinsonism, as well as other associated ailments, in short duration of time.

scholarly journals Metabolic alterations in a Drosophila model of Parkinson's disease based on DJ-1 deficiency

2021 ◽  
Author(s):  
Cristina Solana-Manrique ◽  
Francisco Jose Sanz ◽  
Isabel Torregrosa ◽  
Martina Palomino-Schatzlein ◽  
Carolina Hernandez-Oliver ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Tricarboxylic Acid Cycle ◽  
Therapeutic Targets ◽  
Resonance Spectroscopy ◽  
Metabolic Disturbances ◽  
Metabolic Alterations ◽  
New Biomarkers ◽  
And Control

Parkinson's disease (PD) is the second most common neurodegenerative disorder whose physiopathology is still unclear. Besides, it is urgent to discover new biomarkers and therapeutic targets to facilitate its diagnosis and treatment. Previous studies performed in PD models and samples from PD patients already demonstrated that metabolic alterations were associated with this disease. In this context, the aim of this study is to give a better understanding of metabolic disturbances underlying PD pathogenesis. To achieve this goal, we used a Drosophila PD model based on inactivation of the DJ-1β gene (ortholog of human DJ-1). Metabolomic analyses were performed in 1-day-old and 15-day-old DJ-1β mutants and control flies using 1H nuclear magnetic resonance spectroscopy, combined with expression and enzymatic activity assays of proteins implicated in altered pathways. Our results showed that PD model flies exhibit protein metabolism alterations, a shift from tricarboxylic acid cycle to glycolytic pathway to obtain ATP, together with an increase in the expression of some urea cycle enzymes. Thus, these metabolic changes could be contributing to PD pathogenesis and might constitute possible therapeutic targets and/or biomarkers for this disease.

scholarly journals Marijuana Compounds: A Nonconventional Approach to Parkinson’s Disease Therapy

2016 ◽  
Vol 2016 ◽  
pp. 1-19 ◽  
Author(s):  
Mariana Babayeva ◽  
Haregewein Assefa ◽  
Paramita Basu ◽  
Sanjeda Chumki ◽  
Zvi Loewy
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Unmet Need ◽  
Current Treatment ◽  
Dopamine Neurons ◽  
Significant Research ◽  
Potential Benefits ◽  
Nigrostriatal Dopamine Neurons ◽  
Related Compounds

Parkinson’s disease (PD), a neurodegenerative disorder, is the second most common neurological illness in United States. Neurologically, it is characterized by the selective degeneration of a unique population of cells, the nigrostriatal dopamine neurons. The current treatment is symptomatic and mainly involves replacement of dopamine deficiency. This therapy improves only motor symptoms of Parkinson’s disease and is associated with a number of adverse effects including dyskinesia. Therefore, there is unmet need for more comprehensive approach in the management of PD. Cannabis and related compounds have created significant research interest as a promising therapy in neurodegenerative and movement disorders. In this review we examine the potential benefits of medical marijuana and related compounds in the treatment of both motor and nonmotor symptoms as well as in slowing the progression of the disease. The potential for cannabis to enhance the quality of life of Parkinson’s patients is explored.

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.

SPECT-Befunde bei Hemiparkinson-Syndrom mit 99mTc-HMPAO

1989 ◽  
Vol 28 (03) ◽  
pp. 92-94 ◽  
Author(s):  
C. Neumann ◽  
H. Baas ◽  
R. Hefner ◽  
G. Hör
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Neuronal Activity ◽  
Tracer Uptake ◽  
The Body ◽  
99Mtc Hmpao ◽  
Do So

The symptoms of Parkinson’s disease often begin on one side of the body and continue to do so as the disease progresses. First SPECT results in 4 patients with hemiparkinsonism using 99mTc-HMPAO as perfusion marker are reported. Three patients exhibited reduced tracer uptake in the contralateral basal ganglia One patient who was under therapy for 1 year, showed a different perfusion pattern with reduced uptake in both basal ganglia. These results might indicate reduced perfusion secondary to reduced striatal neuronal activity.

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