Parkinso*

Protein misfolding, aggregation, and fibril formation play a central role in the development of severe neurological disorders, including Alzheimer's and Parkinson's diseases. The structural stability of mature fibrils in these diseases is of great importance, as organisms struggle to effectively eliminate amyloid plaques. To address this issue, it is crucial to investigate the early stages of fibril formation when monomers aggregate into small, toxic, and soluble oligomers. However, these structures are inherently disordered, making them challenging to study through experimental approaches...

INTRODUCTION: Mild cognitive impairment (MCI) is a common symptom observed in individuals with Parkinson's disease (PD) and a main risk factor for progressing to dementia. Our objective was to identify early anatomical brain changes that precede the transition from healthy cognition to MCI in PD. METHODS: Structural T1-weighted magnetic resonance imaging data of PD patients with healthy cognition at baseline were downloaded from the Parkinson's Progression Markers Initiative database...

Parkinson's disease (PD) is a severe, progressive, neurological disorder. PD is not a single disease, but rather resembles a syndrome. PD includes two types of pathogenesis (i.e., classical PD and new PD). Clinically, PD patients present with a range of motor symptoms including decreased spontaneous movement, bradykinesia, muscle rigidity, changes in speech, and resting tremors. PD patients also often exhibit non-motor symptoms such as fatigue, sleep disorders, and emotional and mental health disturbances. Deep brain stimulation (DBS) performed in clinical neurosurgery has demonstrated considerable efficacy in the treatment of dyskinesia that occurs in PD patients...

BACKGROUND: Linear associations between circulating insulin-like growth factor-1 (IGF-1) levels and Parkinson's disease (PD) have been evidenced in observational studies. Yet, the causal relationship between IGF-1 levels and PD remains obscure. We conducted Mendelian randomization to examine the correlation between genetically predicted IGF-1 levels and PD. METHODS: By reviewing genome-wide association studies (GWAS) that are publicly accessible, we uncovered SNPs linked to both serum concentrations of IGF-1 and PD...

Effective treatment of Parkinson's disease (PD), a prevalent central neurodegenerative disorder particularly affecting the elderly population, still remains a huge challenge. We present here a novel nanomedicine formulation based on bioactive hydroxyl-terminated phosphorous dendrimers (termed as AK123) complexed with fibronectin (FN) with anti-inflammatory and antioxidative activities. The created optimized AK123/FN nanocomplexes (NCs) with a size of 223 nm display good colloidal stability in aqueous solution and can be specifically taken up by microglia through FN-mediated targeting...

Epilepsy is one of the most common chronical neurological conditions affecting over 50 million people worldwide. In addition to the stigma and discrimination, individuals with epilepsy suffer from a nearly three-fold increased risk of premature death compared to the general population. Although these premature deaths occur due to multiple causes, sudden unexpected death in epilepsy (SUDEP) still challenges neurologists and clinicians dealing with individuals with epilepsy. Recently, an increased interest in cardiac outcomes related to acute seizures and chronic epilepsy resulted in the groundbreaking development of the "epileptic heart" concept, and sudden cardiac death in individuals with epilepsy, which is 4...

This study reported a case of early-onset parkinsonism associated with a novel variant of the PLA2G6 gene. The boy first started showing symptoms at the age of 11, with gait instability and frequent falls. As the disease progressed, his gait instability worsened, and he developed difficulties with swallowing and speaking, although there was no apparent decline in cognitive function. An MRI of the head revealed significant atrophy of the cerebellum. The initial diagnosis for the boy was early-onset parkinsonism, classified as Hoehn-Yahr grade 5...

Fragment-based drug discovery (FBDD) has emerged as a powerful strategy to confront the challenges faced by conventional drug development approaches, particularly in the context of central nervous system (CNS) disorders. FBDD involves the screening of libraries that comprise thousands of small molecular fragments, each no greater than 300 Da in size. Unlike the generally larger molecules from high-throughput screening that limit customisation, fragments offer a more strategic starting point. These fragments are inherently compact, providing a strong foundation with good binding affinity for the development of drug candidates...

Virtual brain twins are personalized, generative and adaptive brain models based on data from an individual's brain for scientific and clinical use. After a description of the key elements of virtual brain twins, we present the standard model for personalized whole-brain network models. The personalization is accomplished using a subject's brain imaging data by three means: (1) assemble cortical and subcortical areas in the subject-specific brain space; (2) directly map connectivity into the brain models, which can be generalized to other parameters; and (3) estimate relevant parameters through model inversion, typically using probabilistic machine learning...

Neurodegenerative diseases are characterised by neuronal loss and abnormal deposition of pathological proteins in the nervous system. Among the most common neurodegenerative diseases are Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease and transmissible spongiform encephalopathies (TSEs). Sleep and circadian rhythm disturbances are one of the most common symptoms in patients with neurodegenerative diseases. Currently, one of the main objectives in the study of TSEs is to try to establish an early diagnosis, as clinical signs do not appear until the damage to the central nervous system is very advanced, which prevents any therapeutic approach...

BACKGROUND: Double-blind studies have demonstrated that motor complications in Parkinson's disease (PD) can be reduced with continuous delivery of levodopa. The DopaFuse system is a novel, intraoral micropump that attaches to a retainer and uses a propellant to deliver levodopa/carbidopa (LD/CD) continuously into the mouth. OBJECTIVES: Evaluate the safety, pharmacokinetics, and efficacy of LD/CD delivered via the DopaFuse system compared to treatment with intermittent doses of standard oral LD/CD in PD patients with motor fluctuations...

BACKGROUND: Blood pressure control in Parkinson's disease (PD) under subthalamic deep brain stimulation (STN-DBS) is influenced by several intertwined aspects, including autonomic failure and levodopa treatment. OBJECTIVE: To evaluate the effect of chronic STN-DBS, levodopa, and their combination on cardiovascular autonomic functions in PD. METHODS: We performed cardiovascular reflex tests (CRTs) before and 6-months after STN-DBS surgery in 20 PD patients (pre-DBS vs...

BACKGROUND: Tourniquets are common adjuncts in the operating theatre but can be associated with post-operative pain. This study was designed to compare what effect pre-tourniquet Esmarch bandage exsanguination has on pain, compared to pre-tourniquet exsanguination by elevation alone. METHODS: 52 volunteers (104 lower limbs) were included in this study with each volunteer acting as their own matched control. The primary outcome was patient reported pain, measured in both legs simultaneously using area under curve...

The majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) also frequently experience hyposmia. We previously postulated that microglial activation as well as α-synuclein and tau misprocessing can occur during host responses following microbial encounters. Using semiquantitative measurements of immunohistochemical signals, we examined OB and olfactory tract specimens collected serially at autopsies between 2020 and 2023...

BACKGROUND: Ischemic postconditioning (IPostC) has been reported as a promising method for protecting against myocardial ischemia-reperfusion (MI/R) injury. Our previous study found that the infarct-limiting effect of IPostC is abolished in the heart of diabetes whose cardiac expression of DJ-1 (also called PARK7, Parkinsonism associated deglycase) is reduced. However, the role and in particular the underlying mechanism of DJ-1 in the loss of sensitivity to IPostC-induced cardioprotection in diabetic hearts remains unclear...

BACKGROUND: In recent decades, China has experienced a rapid increase in the number of elderly individuals and life expectancy, as well as industrialization, which is associated with an increased prevalence of Parkinson's disease (PD). However, inconsistent results have recently been reported. Therefore, this study aimed to investigate the prevalence and distribution characteristics of PD among individuals aged 45 years and older. METHODS: Using data from the China Health and Retirement Longitudinal Study (CHARLS), we attempted to estimate the prevalence of PD and its distribution characteristics among 19,034 individuals aged 45 years and older residing in 446 communities/villages within 27 provinces/autonomous regions/municipalities in mainland China...

The progression of Parkinson's disease (PD) is heterogeneous across patients, affecting counseling and inflating the number of patients needed to test potential neuroprotective treatments. Moreover, disease subtypes might require different therapies. This work uses a data-driven approach to investigate how observed heterogeneity in PD can be explained by the existence of distinct PD progression subtypes. To derive stable PD progression subtypes in an unbiased manner, we analyzed multimodal longitudinal data from three large PD cohorts and performed extensive cross-cohort validation...

Resilience in neuroscience generally refers to an individual's capacity to counteract the adverse effects of a neuropathological condition. While resilience mechanisms in Alzheimer's disease are well-investigated, knowledge regarding its quantification, neurobiological underpinnings, network adaptations, and long-term effects in Parkinson's disease is limited. Our study involved 151 Parkinson's patients from the Parkinson's Progression Marker Initiative Database with available Magnetic Resonance Imaging, Dopamine Transporter Single-Photon Emission Computed Tomography scans, and clinical information...

Local field potential (LFP) oscillations in the beta band (13-30 Hz) in the subthalamic nucleus (STN) of Parkinson's disease patients have been implicated in disease severity and treatment response. The relationship between single-neuron activity in the STN and regional beta power changes remains unclear. We used spike-triggered average (STA) to assess beta synchronization in STN. Beta power and STA magnitude at the beta frequency range were compared in three conditions: STN versus other subcortical structures, dorsal versus ventral STN, and high versus low beta power STN recordings...

Apart from dopaminergic neurotoxicity, exposure to rotenone, a commonly used insecticide in agriculture, also adversely affects hippocampal and cortical neurons, resulting in cognitive impairments in mice. We recently established a role of microglia-mediated neuroinflammation in rotenone-elicited deficits of cognition, yet the mechanisms remain elusive. Here, we investigated the involvement of NADPH oxidase 2 (NOX2) catalytic subunit gp91phox in rotenone-induced cognitive deficits and the associated mechanisms...