Parkinson

Abnormal accumulation of alpha-synuclein (αSyn) in the remaining nigra dopaminergic neurons is a common neuropathological feature found in patients with Parkinson's disease (PD). Antibody-based immunotherapy has been considered a potential approach for PD treatment. This study aims to investigate the effectiveness of active immunization against αSyn in a mouse model of PD. Adult mice were immunized with or without a synthetic peptide containing the C-terminal residues of human αSyn and activation epitopes, followed by an intranigral injection of adeno-associated virus vectors for overexpressing human αSyn...

OBJECTIVE: Closed-loop deep brain stimulation (DBS) approaches proposed for Parkinson's disease (PD) have considered modulation of a selected stimulation parameter to control a single biomarker. While promising performance has been demonstrated for symptoms well-correlated with the chosen biomarker, suboptimal regulation can occur for uncorrelated symptoms or when the relationship between biomarker and symptoms varies. Similarly, control of stimulation-induced side-effects is typically not considered...

The vesicular monoamine transporter 2 (VMAT2) is a proton-dependent antiporter responsible for loading monoamine neurotransmitters into synaptic vesicles. Dysregulation of VMAT2 can lead to several neuropsychiatric disorders including Parkinson's disease and schizophrenia. Furthermore, drugs such as amphetamine and MDMA are known to act on VMAT2, exemplifying its role in the mechanisms of actions for drugs of abuse. Despite VMAT2's importance, there remains a critical lack of mechanistic understanding, largely driven by a lack of structural information...

Neurodegenerative disorders represent a major and growing healthcare challenge globally. Among the numerous molecular pathways implicated in their pathogenesis, calpain signaling has emerged as a crucial player in neuronal dysfunction and cell death. Calpain is a family of calcium-dependent cysteine proteases that is involved in many biological processes, such as signal transduction, cytoskeleton remodeling, and protein turnover. Dysregulation of calpain activation and activity has been associated with several neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases...

Parkinson's disease (PD) is the second-most common neurodegenerative disease and is largely caused by the death of dopaminergic (DA) cells. Dopamine loss occurs in the substantia nigra pars compacta and leads to dysfunctions in motor functions. Death of DA cells can occur with oxidative stress and dysfunction of glial cells caused by Parkinson-related gene mutations. Lactoferrin (Lf) is a multifunctional glycoprotein that is usually known for its presence in milk, but recent research shows that Lf is also found in the brain regions...

Tremor is a common symptom among all stages of Parkinson's Disease (PD) patients. To measure daily tremor events, we utilized IMU sensing data from wrists while PD patients were drawing. We secured 30 patients' IMU sensing data, following standard rating scale activities. With the collected data, we conducted data analysis for identifying any tremor episodes and extracting tremor amplitude. Our preliminary analysis and results show the potential of measuring kinetic tremors effectively. We plan to further analyze tremor events of PD patients via wearable sensing devices...

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Increasing evidence highlights that excessive iron accumulation in the brain plays a vital role in neuronal senescence and is implicated in the pathogenesis of age-related neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Therefore, the chemical compounds that eliminate an iron overload may provide better protection against oxidative stress conditions that cause the accumulation of senescent cells during brain aging. Ebselen has been identified as a strongly useful compound in the research on redox biology mechanisms...

Exposure to carbon disulfide (CS2 ) has been associated with an increased incidence of parkinsonism in workers, but the mechanism underlying this association remains unclear. Using a rat model, we investigated the effects of chronic CS2 exposure on parkinsonian pathology. Our results showed that CS2 exposure leads to significant motor impairment and neuronal damage, including loss of dopaminergic neurons and degeneration of the substantia nigra pars compacta (SNpc). The immunoassays revealed that exposure to CS2 induces aggregation of α-synuclein and phosphorylated α-synuclein, as well as activation of necroptosis in the SNpc...

Parkinson's disease (PD) is a chronic neurodegenerative disease (NDD) due to the degeneration of dopaminergic neurons (DNs) in the substantia nigra (SN). PD is characterized by diverse motor symptoms such as rigidity, resting tremors, and bradykinesia, and non-motor symptoms such as cognitive dysfunction and sleep disturbances. Vitamin D (VD), VD receptor (VDR), and VD metabolites are present in the brain and play a role in maintaining the development, differentiation, and functions of the DNs. VDRs exert protective effects against PD neuropathology by modulating functional capacity and DNs neurotransmission in the SN...

BACKGROUND Prion disease (PrD) is one of the rapidly progressive dementias. It typically requires several diagnostic criteria to fulfill a probable diagnosis, as definite diagnosis is based on isolated brain biopsy. There has been much debate on a possible infectious etiology of PrD. Viral infections are commonly pathologic in most neurodegenerative conditions. In PrD, misfolded proteins can be contagious and act as infective proteins, regardless of the pathologic agent. There is evidence that COVID-19 can result in neurologic manifestations, and neurodegeneration has been reported in the literature...

Protein quality control pathways ensure a functional proteome and rely on a complex proteostasis network (PN) that is composed of molecular chaperones and proteases. Failures in the PN can lead to a broad spectrum of diseases, including neurodegenerative disorders like Alzheimer's, Parkinson's, and a range of motor neuron diseases. The EMBO workshop "Protein quality control: from molecular mechanisms to therapeutic intervention" covered all aspects of protein quality control from underlying molecular mechanisms of chaperones and proteases to stress signaling pathways and medical implications...

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. The pathological hallmark of PD is the appearance of intraneuronal cytoplasmic α-synuclein (α-Syn) aggregation, called Lewy bodies. α-Syn aggregation is deeply involved in the pathogenesis of PD. Oxidative stress is also associated with the progression of PD. In the present study, to investigate whether a hypoxia-inducible factor (HIF)-prolyl hydroxylase (PH) inhibitor, FG-4592 (also called roxadustat), has neuroprotective effects against α-Syn-induced neurotoxicity, we employed a novel α-Syn stably expressing cell line (named α-Syn-N2a cells) utilizing a piggyBac transposon system...

The mutations on microtubule associated protein tau (MAPT) gene manifest clinically with behavioural frontotemporal dementia (FTD), parkinsonism, such as progressive supranuclear palsy and corticobasal degeneration, and rarely with amyotrophic lateral sclerosis (ALS). FTD-parkinsonism and FTD-ALS are clinical overlaps included in the spectrum of MAPT mutation's phenotypes. The mutations on MAPT gene cause the dysfunction of tau protein determining its accumulation in neurofibrillary tangles. Recent data describe frequently the co-occurrence of the aggregation of tau protein and α-synuclein in patients with parkinsonism and Parkinson disease (PD), suggesting an interaction of the two proteins in determining neurodegenerative process...

Chronic neuroinflammation is implicated in the pathogenesis of Parkinson's disease (PD), one of the most common neurodegenerative diseases. Itaconate, an endogenous metabolite derived from the tricarboxylic acid cycle via immune-responsive gene 1 activity, may mediate anti-inflammatory responses by activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway. This study investigates the neuroprotective potential of 4-octyl itaconate (OI), a cell-permeable derivative of itaconate, in cellular models of PD...

BACKGROUND: Astrocytes have recently gained attention as key contributors to the pathogenesis of neurodegenerative disorders including Parkinson's disease. To investigate human astrocytes in vitro, numerous differentiation protocols have been developed. However, the properties of the resulting glia are inconsistent, which complicates the selection of an appropriate method for a given research question. Thus, we compared two approaches for the generation of iPSC-derived astrocytes. We phenotyped glia that were obtained employing a widely used long, serum-free ("LSF") method against an in-house established short, serum-containing ("SSC") protocol which allows for the generation of astrocytes and midbrain neurons from the same precursor cells...

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and often fatal neurodegenerative disease characterized by the loss of Motor Neurons (MNs) in spinal cord, motor cortex and brainstem. Despite significant efforts in the field, the exact pathogenetic mechanisms underlying both familial and sporadic forms of ALS have not been fully elucidated, and the therapeutic possibilities are still very limited. Here we investigate the molecular mechanisms of neurodegeneration induced by chronic exposure to the environmental cyanotoxin L-BMAA, which causes a form of ALS/Parkinson's disease (PD) in several populations consuming food and/or water containing high amounts of this compound...

INTRODUCTION: Parkinsonism is now recognized as an additional feature in RFC1/CANVAS syndrome; however, no systematic evaluation of nigrostriatal dopaminergic function has been published so far. METHODS: This is an observational, single-center study, which analyzed 13 patients with molecular confirmation of RFC1/CANVAS. Disease severity was assessed with the SARA scale. Each subject was carefully evaluated for the presence of parkinsonian features. Dopamine transporter (DAT) imaging was acquired and reconstructed in the transverse, coronal and sagittal planes 4 h after venous injection of 99mTc-TRODAT-1...

The aggregation of the disordered neuronal protein, α-Synuclein (αS), is the primary pathological feature of Parkinson's disease. Current hypotheses favor cell-to-cell spread of αS species as underlying disease progression, driving interest in identifying the molecular species and cellular processes involved in cellular internalization of αS. Prior work from our lab identified the chemically specific interaction between αS and the pre-synaptic adhesion protein neurexin 1β (N1β) to be capable of driving cellular internalization of both monomer and aggregated forms of αS...

INTRODUCTION: Within clinical neuropsychology, a classic diagnostic distinction is made between cortical and subcortical disorders, especially based on their memory profiles. Typically, this is based on the comparison of recall and recognition trials, where individuals with cortical conditions do not tend to benefit (i.e., score well) on recognition trials and individuals with subcortical conditions do. Although the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a widely used brief cognitive battery, there is a lack of evidence to support this measure's utility in distinguishing between the memory profiles of these conditions...