Parkinsonism

Alcohol consumption significantly impacts disease burden and has been linked to various diseases in observational studies. However, comprehensive meta-analyses using Mendelian randomization (MR) to examine drinking patterns are limited. We aimed to evaluate the health risks of alcohol use by integrating findings from MR studies. A thorough search was conducted for MR studies focused on alcohol exposure. We utilized two sets of instrumental variables-alcohol consumption and problematic alcohol use-and summary statistics from the FinnGen consortium R9 release to perform de novo MR analyses...

Levodopa (LD) has been the most efficacious medication and the gold standard therapy for Parkinson's disease (PD) for decades. However, its long-term administration is usually associated with motor complications, which are believed to be the result of the fluctuating pharmacokinetics of LD following oral administration. Duodopa® is the current option to offer a continuous delivery of LD and its decarboxylase inhibitor carbidopa (CD); however, its administration involves invasive surgical procedures, which could potentially lead to lifelong complications, such as infection...

Despite the extensive research successes and continuous developments in modern medicine in terms of diagnosis, prevention, and treatment, the lack of clinically useful disease-modifying drugs or immunotherapeutic agents that can successfully treat or prevent neurodegenerative diseases is an ongoing challenge. To date, only one of the 244 drugs in clinical trials for the treatment of neurodegenerative diseases has been approved in the past decade, indicating a failure rate of 99.6%. In corollary, the approved monoclonal antibody did not demonstrate significant cognitive benefits...

The treatment of Parkinson's disease has been moving into the focus of pharmaceutical development. Yet, the necessity for reliable model systems in the development phase has made research challenging and in vivo models necessary. We have established reliable, reproducible in vitro model systems to evaluate the binding and transport of dopamine-loaded PLGA nanoparticles for the treatment of Parkinson's disease and put the results in context with comparable in vivo results. The in vitro models have provided similar results concerning the usability of the investigated nanoparticles as the previously used in vivo models and thus provide a good alternative in line with the 3R principles in pharmaceutical research...

Neurodegenerative disorders (NDs) include a range of chronic conditions characterized by progressive neuronal loss, leading to cognitive, motor, and behavioral impairments. Common examples include Alzheimer's disease (AD) and Parkinson's disease (PD). The global prevalence of NDs is on the rise, imposing significant economic and social burdens. Despite extensive research, the mechanisms underlying NDs remain incompletely understood, hampering the development of effective treatments. Excitotoxicity, particularly glutamate-mediated excitotoxicity, is a key pathological process implicated in NDs...

Early-morning off periods, causing early-morning akinesia, can lead to significant motor and nonmotor morbidity in levodopa-treated fluctuating Parkinson's disease (PD) cases. Despite validated bedside scales in clinical practice, such early-morning off periods may remain undetected unless specific wearable technologies, such as the Parkinson's KinetiGraph™ (PKG) watch, are used. We report five PD cases for whom the PKG detected early-morning off periods that were initially clinically undetected and as such, untreated...

This study delves into the multifaceted approaches to treating Parkinson's disease (PD), a neurodegenerative disorder primarily affecting motor function but also manifesting in a variety of symptoms that vary greatly among individuals. The complexity of PD symptoms necessitates a comprehensive treatment strategy that integrates surgical interventions, pharmacotherapy, and physical therapy to tailor to the unique needs of each patient. Surgical options, such as deep brain stimulation (DBS), have been pivotal for patients not responding adequately to medication, offering significant symptom relief...

Background: Hearing loss has been recognized as a risk factor for dementia and non-motor features of Parkinson's disease (PD). The apolipoprotein E (APOE) protein contributes to maintenance and repair of neuronal cell membranes, causing age-related disorders. This study aimed to analyze the impact of hearing loss on cognitive impairment, PD severity, and APOE gene expression in these patients. Methods: A total of 72 out-patients diagnosed with either PD or hearing loss were enrolled in this study. The hearing assessment included pure-tone audiometry, speech reception thresholds, and speech discrimination ability...

Neurodegenerative diseases such as dementia and Parkinson's disease pose significant challenges to older adults globally. While pharmacological treatments remain primary, increasing evidence supports the role of non-pharmacological strategies like physical activity in managing these conditions. This systematic review critically evaluates the effectiveness of Nursing based physical activity interventions in improving cognitive function, physical functioning, mobility, and overall quality of life among older adults with neurodegenerative diseases...

Background : This is a retrospective longitudinal study comparing 374 patients with Parkinson's disease (PD) who were treated in centers offering a specialized program of enhanced rehabilitation therapy in addition to expert outpatient care to 387 patients with PD, who only received expert outpatient care at movement disorders centers in Italy. Methods : The data are from subjects recruited in the Parkinson's Outcome Project (POP) at six Italian centers that are part of a multicenter collaboration for care quality improvement (the Fresco Network)...

Compound 7-16 was designed and synthesized in our previous study and was identified as a more potential selective 5-HT2A receptor antagonist and inverse agonist for treating Parkinson's disease psychosis (PDP). Then, the metabolism, disposition, and excretion properties of 7-16 and its potential inhibition on transporters were investigated in this study to highlight advancements in the understanding of its therapeutic mechanisms. The results indicate that a total of 10 metabolites of 7-16/[14 C]7-16 were identified and determined in five species of liver microsomes and in rats using UPLC-Q Exactive high-resolution mass spectrometry combined with radioanalysis...

Children living in rural and migrant areas in the United States disproportionately suffer from poor oral health. Additionally, there continues to be a shortage of pediatric dentists practicing in rural/migrant areas. The purpose of this formative research study was to assess whether staff, teachers and families from rural/migrant Head Start/Early Head Start (HS/EHS) programs in California were receptive to oral health online education workshops conducted by pediatric dental residents who were assisted by bilingual (English and Spanish) community oral health workers (COHWs)...

In the area of drug research, several computational drug repurposing studies have highlighted candidate repurposed drugs, as well as clinical trial studies that have tested/are testing drugs in different phases. To the best of our knowledge, the aggregation of the proposed lists of drugs by previous studies has not been extensively exploited towards generating a dynamic reference matrix with enhanced resolution. To fill this knowledge gap, we performed weight-modulated majority voting of the modes of action, initial indications and targeted pathways of the drugs in a well-known repository, namely the Drug Repurposing Hub...

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Given its prevalence, reliable biomarkers for early diagnosis are required. Exosomal proteins within extracellular nanovesicles are promising candidates for diagnostic, screening, prognostic, and disease monitoring purposes in neurological diseases such as PD. This review aims to evaluate the potential of extracellular vesicle proteins or miRNAs as biomarkers for PD. A comprehensive literature search until January 2024 was conducted across multiple databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, to identify relevant studies reporting exosome biomarkers in blood samples from PD patients...

Chronic environmental exposure to toxic heavy metals, which often occurs as a mixture through occupational and industrial sources, has been implicated in various neurological disorders, including Parkinsonism. Vanadium pentoxide (V2 O5 ) typically presents along with manganese (Mn), especially in welding rods and high-capacity batteries, including electric vehicle batteries; however, the neurotoxic effects of vanadium (V) and Mn co-exposure are largely unknown. In this study, we investigated the neurotoxic impact of MnCl2 , V2 O5, and MnCl2 -V2 O5 co-exposure in an animal model...

The NR4A2 gene encodes an orphan transcription factor of the steroid-thyroid hormone-retinoid receptor superfamily. This review focuses on the clinical findings associated with the pathogenic variants so far reported, including three unreported cases. Also, its role in neurodegenerative diseases, such as Parkinson's or Alzheimer's disease, is examined, as well as a brief exploration on recent proposals to develop novel therapies for these neurological diseases based on small molecules that could modulate NR4A2 transcriptional activity...

Parkinson's disease (PD) is a progressive disorder characterized by the apoptosis of dopaminergic neurons in the basal ganglia. This study explored the potential effects of aminophylline, a non-selective adenosine A1 and A2A receptor antagonist, on catalepsy and gait in a haloperidol-induced PD model. Sixty adult male Swiss mice were surgically implanted with guide cannulas that targeted the basal ganglia. After seven days, the mice received intraperitoneal injections of either haloperidol (experimental group, PD-induced model) or saline solution (control group, non-PD-induced model), followed by intracerebral infusions of aminophylline...

While primarily produced in the pineal gland, melatonin's influence goes beyond its well-known role in regulating sleep, nighttime metabolism, and circadian rhythms, in the field of chronobiology. A plethora of new data demonstrates melatonin to be a very powerful molecule, being a potent ROS/RNS scavenger with anti-inflammatory, immunoregulatory, and oncostatic properties. Melatonin and its metabolites exert multiple beneficial effects in cutaneous and systemic aging. This review is focused on the neuroprotective role of melatonin during aging...

Polymerase I (Pol I) is at the epicenter of ribosomal RNA (rRNA) synthesis. Pol I is a target for the treatment of cancer. Given the many cellular commonalities between cancer and neurodegeneration (i.e., different faces of the same coin), it seems rational to consider targeting Pol I or, more generally, rRNA synthesis for the treatment of disorders associated with the death of terminally differentiated neurons. Principally, ribosomes synthesize proteins, and, accordingly, Pol I can be considered the starting point for protein synthesis...

Parkinson's disease (PD), a progressive neurodegenerative disease, has no cure, and current therapies are not effective at halting disease progression. The disease affects mid-brain dopaminergic neurons and, subsequently, the spinal cord, contributing to many debilitating symptoms associated with PD. The GTP-binding protein, Rho, plays a significant role in the cellular pathology of PD. The downstream effector of Rho, Rho-associated kinase (ROCK), plays multiple functions, including microglial activation and induction of inflammatory responses...