BCKDK loss impairs mitochondrial Complex I activity and drives alpha-synuclein aggregation in models of Parkinson's disease.

Mitochondrial dysfunction and α-synuclein (αSyn) aggregation are key contributors to Parkinson's Disease (PD). While genetic and environmental risk factors, including mutations in mitochondrial-associated genes, are implicated in PD, the precise mechanisms linking mitochondrial defects to αSyn pathology remain incompletely understood, hindering the development of effective therapeutic interventions. Here, we identify the loss of branched chain ketoacid dehydrogenase kinase (BCKDK) as a mitochondrial risk factor that exacerbates αSyn pathology by disrupting Complex I function.

Theta-Gamma Decoupling - A neurophysiological marker of impaired reward processing in Parkinson's disease.

Individuals with Parkinson's disease (PD) exhibit altered reward processing, reflected by a decreased amplitude of an event-related potential (ERP) marker called reward positivity (RewP). Most studies have used RewP to investigate reward behavior due to the high temporal resolution of EEG and its high sensitivity. However, traditional single-electrode ERP analyses often overlook the intricate dynamics of non-phase-locked oscillatory activity and the complex interactions within these neural oscillatory patterns.

Tetrahydrofolic acid accelerates amyloid fibrillization, decreases cytotoxic oligomers and suppresses their toxicity.

Soluble cytotoxic oligomers produced during the fibrillation of both α-synuclein (αS) and amyloid-β protein (Aβ) are key pathogenic factors in Parkinson's disease (PD) and Alzheimer's disease (AD). Reducing toxic oligomers by regulating the aggregation process of αS and Aβ is an important strategy for the treatment of PD and AD. Herein, tetrahydrofolic acid (THF) is found to accelerate amyloid fibrillization, decreases cytotoxic oligomers and suppresses their toxicity.

Hydroxycinnamic acids mediated modulation of α-Synuclein fibrillation: Biophysical insights.

The fibrillation of α-synuclein (α-Syn) is considered a major contributor to Parkinson's disease (PD). Recent therapeutic measures have focused on inhibiting the fibrillation of α-Syn using various small molecules. We report here the effects of two different hydroxycinnamic acids; chlorogenic acid and sinapic acid on α-Syn fibrillation and have also discussed the mechanistic insights into their mode of modulation.

Alpha-synuclein RT-QuIC assay in gastroduodenal and skin biopsies of Parkinson disease patients.

In this study, we compared the value of pathological alpha-synuclein (αSyn) seed amplification assay (SAA) in gastric and duodenal biopsies with skin biopsies in Parkinson disease (PD) patients with different disease duration. The accuracy of αSyn SAA was 87.7% in skin, 67.

Dopaminergic Treatment and Episodic Memory in Parkinson's Disease: A Meta-analysis of the Literature.

To date, few studies have focused on the benefits of dopaminergic treatment on episodic memory functions in patients affected by Parkinson's disease (PD). We conducted a meta-analysis to determine the effects of pharmacological therapy with dopamine in alleviating episodic memory deficits in Parkinson's patients. A secondary aim was to evaluate the role of dopamine in episodic memory circuits and thus in different memory systems.

Atrial Tachyarrhythmias With Ultra-Rapid Ventricular Response and Sudden Death in Patients Without Structural Heart Disease.

Background: Sudden cardiac death (SCD) is generally associated with life-threatening ventricular arrhythmias. Supraventricular arrhythmias are an accepted cause of SCD in Wolff-Parkinson-White syndrome and complex congenital heart disease. However, the role of atrial tachyarrhythmias (ATAs) in SCD in patients with structurally normal hearts is unclear.

Propranolol Reduces Parkinson's Tremor and Inhibits Tremor-Related Activity in the Motor Cortex: A Placebo-Controlled Crossover Trial.

Objective: Parkinson's disease (PD) resting tremor is thought to be initiated in the basal ganglia and amplified in the cerebello-thalamo-cortical circuit. Because stress worsens tremor, the noradrenergic system may play a role in amplifying tremor. We tested if and how propranolol, a non-selective beta-adrenergic receptor antagonist, reduces PD tremor and whether or not this effect is specific to stressful conditions.

Overexpression of α-synuclein in PDF neurons alters sleep-wake pattern by regulating lipid metabolism in Drosophila.

Parkinson's disease (PD) is a complex neurodegenerative disorder, characterized by the aggregation of α-synuclein (α-syn). Current research increasingly indicates the prevalence of sleep-wake disorders in early-stage PD, although the underlying pathogenic mechanisms remain unclear. In this study, transgenic Drosophila models were utilized to observe excessive daytime sleepiness and impaired anticipation in flies overexpressing α-syn in pan-neurons and circadian clock neurons.

Subthalamic γ Oscillation Underlying Rapid Eye Movement Sleep Abnormality in Parkinsonian Patients.

Background: Abnormal rapid eye movement (REM) sleep, including REM sleep behavior disorder (RBD) and reduced REM sleep, is common in Parkinson's disease (PD), highlighting the importance of further study on REM sleep. However, the biomarkers of REM disturbances remain unknown, leading to the lack of REM-specific neuromodulation interventions.

Objective: This study aims to investigate the neurophysiological biomarkers of REM disturbance in parkinsonian patients.

Enhanced gait tracking measures for individuals with stroke using leg-worn inertial sensors.

Background: Clinical gait analysis plays a pivotal role in diagnosing and treating walking impairments. Inertial measurement units (IMUs) offer a low-cost, portable, and practical alternative to traditional gait analysis equipment, making these techniques more accessible beyond specialized clinics. Previous work and algorithms developed for specific clinical populations, like in individuals with Parkinson's disease, often do not translate effectively to other groups, such as stroke survivors, who exhibit significant variability in their gait patterns.

Effects of Stigmatizing Language on Trainees' Clinical Decision-Making in Substance Use Disorders: A Randomized Controlled Trial.

Objectives: Substance use disorder (SUD) continues to be one of the most stigmatized and under-treated conditions in the United States. Stigmatizing language used by healthcare workers can transmit bias to others within healthcare, including medical trainees. This study investigates how stigmatizing language and undergraduate medical education (UME) curricula may influence trainees' clinical decision-making for patients with SUD.

Hormonal mechanisms in the paraventricular nuclei associated with hyperalgesia in Parkinson's disease model rats.

Pain is a major non-motor symptom of Parkinson's disease (PD). The relationship between hyperalgesia and neuropeptides originating from paraventricular nucleus (PVN) in 6-hydroxydopamine (6-OHDA) rats has already been investigated for oxytocin (OXT), but not yet for arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH). The present study aimed to investigate the alterations in these neuropeptides following nociceptive stimulation in PD model rats and to examine the mechanisms of hyperalgesia.

Short-term cognitive practice effects in Parkinson's disease: More than meets the eye.

Introduction: Although practice effects (PE) on repeated cognitive testing have received growing interest in Alzheimer's disease, they have been understudied in Parkinson's disease (PD). The current paper examined PE across one week in a sample of patients with PD via traditional methods and regression-based change scores, as well as if these change scores relate to clinical variables in PD.

Methods: Thirty-five patients with PD were administered a brief cognitive battery twice across approximately one week.

Membrane vesicles from lactobacillus acidophilus reduce intestinal inflammation and increase 5-HT in the substantia nigra of rats with parkinson's disease.

Background: This study aimed to investigate the role of membrane vesicles (MVs) from the probiotic Lactobacillus acidophilus in reducing intestinal inflammation and increasing 5-hydroxytryptamine (5-HT) and tyrosine hydroxylase (TH) in the substantia nigra in the 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease (PD).

Methods: Twenty healthy male Wistar rats were randomly assigned to four groups (n = 5 per group), including a) control, b) 6-OHDA, c) 6-OHDA+MV, and d) sham groups. PD was induced by bilateral injection of 6-OHDA.

Sleep spindle variation in patients with Parkinson's disease on first nights of sub-optimal deep brain stimulation.

Objective: Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) is a common treatment for motor symptoms of Parkinson's disease but its influence on non-motor symptoms is less clear. Sleep spindles are known to be reduced in patients with Parkinson's disease, but the effect of STN DBS is unknown. The objective of our study was to address this knowledge gap.

Recent advances in stem cell therapy: efficacy, ethics, safety concerns, and future directions focusing on neurodegenerative disorders - a review.

Neurodegeneration refers to the gradual loss of neurons and extensive changes in glial cells like tau inclusions in astrocytes and oligodendrocytes, α-synuclein inclusions in oligodendrocytes and SOD1 aggregates in astrocytes along with deterioration in the motor, cognition, learning, and behavior. Common neurodegenerative disorders are Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), spinocerebellar ataxia (SCA), and supranuclear palsy. There is a lack of effective treatment for neurodegenerative diseases, and scientists are putting their efforts into developing therapies against them.

In-depth mass-spectrometry reveals phospho-RAB12 as a blood biomarker of G2019S LRRK2-driven Parkinson's disease.

Leucine-rich repeat kinase 2 (LRRK2) inhibition is a promising disease-modifying therapy for LRRK2-associated Parkinson's disease (L2PD) and idiopathic PD (iPD). However, pharmaco-dynamic readouts and progression biomarkers for clinical trials aiming for disease modification are insufficient since no endogenous marker reflecting enhanced kinase activity of the most common LRRK2 G2019S mutation has been reported yet in L2PD patients. Employing phospho-/proteomic analyses we assessed the impact that LRRK2 activating mutations had in peripheral blood mononuclear cells (PBMCs) from a LRRK2 clinical cohort from Spain (n=174).

Single-Vesicle Electrochemistry in Fresh Brain Slices Enables In Situ Quantification of Vesicular Monoamine.

The quantitative analysis of vesicular neurotransmitters in neurons in situ is paramount for investigating neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease (PD). Unfortunately, a direct approach for monitoring neurotransmitter chemistry in single vesicles in fresh brain tissue has remained inaccessible so far. Here, we introduce an innovative platform of single-vesicle electrochemistry (SVE) in fresh brain tissue, enabling the quantification of neurotransmitters at the single-vesicle level for both soma and varicosity.

The limbic and extra-limbic encephalitis associated with glutamic acid decarboxylase (GAD)-65 antibodies: an observational study.

We aimed to define the clinical features and outcomes of encephalitis associated with anti-GAD65 Abs. In addition, we reviewed cases published in the literature with GAD65 encephalitis. We retrospectively studied 482 consecutive patients attending a tertiary care center for evaluation of an autoimmune neurological disorder.