The evolution of tremor in Parkinson's Disease: insights from a 4-year longitudinal assessment.

Introduction: While tremor is considered a cardinal motor sign in patients with Parkinson's disease (PD), little is known about the evolution of the different types of PD tremor over time.

Aims: Our objectives were to assess the rate of progression of the various types of PD tremor over the disease course and to verify if the presence of different tremors is consistently associated with specific motor and non-motor burdens over time. Finally, we investigated whether the presence of different tremors can predict specific trajectories of disease progression.

GATA Transcription Factors: A Cross-Road for Erythropoiesis, Neurodevelopment, and Synucleinopathies.

Alpha-synuclein (α-syn), a 140 amino acid protein, is abundantly expressed in the central nervous system (CNS) and in the erythrocytes, playing a pivotal role in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies. Among the GATA family transcription factors (TFs), GATA1 and GATA2 regulate the meg-erythrocytic differentiation starting from the hematopoietic stem cell. In erythropoiesis, the GATA1-2 switching regulates the expression of the α-syn gene (SNCA) in the erythrocytes, which is essential for iron metabolism and membrane stability.

Salivary biomarkers for the molecular diagnosis of dementia with Lewy bodies.

BackgroundDespite dementia with Lewy bodies (DLB) being the second most common form of neurodegenerative dementia, more than 80% of DLB cases are initially misdiagnosed. Alpha-synuclein (a-syn) and tau species have been detected in peripheral tissues and biological fluids of DLB patients and among different biological fluids, saliva represent an easely accessible and non-invasive source for biomarker detection.ObjectiveThis study aimed to investigate salivary a-syn and tau species as molecular disease biomarkers, assessing their potential in the diagnosis of DLB and in the differential diagnosis on respect to Alzheimer's disease (AD) and Parkinson's disease (PD).

Proteopathic seed amplification assays in easily accessible specimens for human synucleinopathies, tauopathies, and prionopathies: A scoping review.

A hallmark event in neurodegenerative diseases is represented by the misfolding, aggregation and accumulation of proteins, leading to cellular and network dysfunction preceding the development of clinical symptoms by years. Early diagnosis represents a crucial issue in the field of neuroscience as it offers the potential to utilize this therapeutic window in the future to manage disease-modifying therapy. Seed amplification assays, including Real-Time Quaking-Induced Conversion (RT-QuIC) and Protein Misfolding Cyclic Amplification (PMCA), have emerged in recent years as innovative techniques developed to detect minute amounts of amyloidogenic proteins.

Association of Early fMRI Connectivity Alterations With Different Cognitive Phenotypes in Patients With Newly Diagnosed Parkinson Disease.

Background And Objectives: According to the dual syndrome hypothesis, patients with Parkinson disease (PD) with visuospatial deficits are more likely to progress to dementia, compared with patients with a prevalent dysexecutive syndrome. In this study, we aimed to investigate whether early connectivity changes in the dorsolateral prefrontal cortex (DLPFC) and the precuneus (PCun)-which are critical to fronto-executive and visuospatial functions, respectively-can identify distinct cognitive phenotypes in cognitively intact newly diagnosed patients with PD.

Methods: Newly diagnosed, drug-naïve patients with PD (≤2 years from clinical onset) with normal Montreal Cognitive Assessment (MoCA), were consecutively enrolled from our Movement Disorders Clinics in Italy.

TNBS colitis induces architectural changes and alpha-synuclein overexpression in mouse distal colon: A morphological study.

Alpha-synuclein (α-syn) is widely expressed in presynaptic neuron terminals, and its structural alterations play an important role in the pathogenesis of Parkinson's disease (PD). Aggregated α-syn has been found in brain, in the peripheral nerves of the enteric nervous system (ENS) and in the intestinal neuroendocrine cells during synucleinopathies and inflammatory bowel disorders. In the present study, we evaluated the histomorphological features of murine colon with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, a common model of colitis.

Neurophysiological Features of Tremor during Walking in Parkinson's Disease.

Background: In Parkinson's Disease (PD), upper limb tremor during walking (TW) is observed and clinical observations suggest it may represent a variant of rest tremor. However, its neurophysiological characteristics remain unexplored.

Objectives: This study compared the neurophysiological features of TW with other PD tremors and tested whether TW arises from reduced ipsilateral arm swing.

α-Synuclein oligomers form by secondary nucleation.

Oligomeric species arising during the aggregation of α-synuclein are implicated as a major source of toxicity in Parkinson's disease, and thus a major potential drug target. However, both their mechanism of formation and role in aggregation are largely unresolved. Here we show that, at physiological pH and in the absence of lipid membranes, α-synuclein aggregates form by secondary nucleation, rather than simple primary nucleation, and that this process is enhanced by agitation.

Interaction between α-Synuclein and Bioactive Lipids: Neurodegeneration, Disease Biomarkers and Emerging Therapies.

The present review provides a comprehensive examination of the intricate dynamics between α-synuclein, a protein crucially involved in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease and multiple system atrophy, and endogenously-produced bioactive lipids, which play a pivotal role in neuroinflammation and neurodegeneration. The interaction of α-synuclein with bioactive lipids is emerging as a critical factor in the development and progression of neurodegenerative and neuroinflammatory diseases, offering new insights into disease mechanisms and novel perspectives in the identification of potential biomarkers and therapeutic targets. We delve into the molecular pathways through which α-synuclein interacts with biological membranes and bioactive lipids, influencing the aggregation of α-synuclein and triggering neuroinflammatory responses, highlighting the potential of bioactive lipids as biomarkers for early disease detection and progression monitoring.

Mapping Motor Cortical Network Excitability and Connectivity Changes in De Novo Parkinson's Disease.

Background: Transcranial magnetic stimulation-electroencephalography (TMS-EEG) has demonstrated decreased excitability in the primary motor cortex (M1) and increased excitability in the pre-supplementary motor area (pre-SMA) in moderate-advanced Parkinson's disease (PD).

Objectives: The aim was to investigate whether these abnormalities are evident from the early stages of the disease, their behavioral correlates, and relationship to cortico-subcortical connections.

Methods: Twenty-eight early, drug-naive (de novo) PD patients and 28 healthy controls (HCs) underwent TMS-EEG to record TMS-evoked potentials (TEPs) from the primary motor cortex (M1) and the pre-SMA, kinematic recording of finger-tapping movements, and a 3T-MRI (magnetic resonance imaging) scan to obtain diffusion tensor imaging (DTI) reconstruction of white matter (WM) tracts connecting M1 to the ventral lateral anterior thalamic nucleus and pre-SMA to the anterior putamen.

Single-molecule characterization of salivary protein aggregates from Parkinson's disease patients: a pilot study.

Saliva is a convenient and accessible biofluid that has potential as a future diagnostic tool for Parkinson's disease. Candidate diagnostic tests for Parkinson's disease to date have predominantly focused on measurements of α-synuclein in CSF, but there is a need for accurate tests utilizing more easily accessible sample types. Prior studies utilizing saliva have used bulk measurements of salivary α-synuclein to provide diagnostic insight.

Evaluating the Diagnostic Potential of Combined Salivary and Skin Biomarkers in Parkinson's Disease.

Oligomeric alpha-synuclein (α-syn) in saliva and phosphorylated α-syn deposits in the skin have emerged as promising diagnostic biomarkers for Parkinson's disease (PD). This study aimed to assess and compare the diagnostic value of these biomarkers in discriminating between 38 PD patients and 24 healthy subjects (HSs) using easily accessible biological samples. Additionally, the study sought to determine the diagnostic potential of combining these biomarkers and to explore their correlations with clinical features.

The chronic use of serotonin norepinephrine reuptake inhibitors facilitates dyskinesia priming in early Parkinson's disease.

Background: Parkinson's disease (PD) patients are frequently exposed to antidepressant medications (ADMs). Norepinephrine (NE) and serotonin (5HT) systems have a role in levodopa-induced dyskinesias (LID) pathophysiology.

Methods: We performed a longitudinal analysis on the PPMI cohort including drug-naïve PD patients, who are progressively exposed to dopamine replacement therapies (DRTs) to test the effect of ADM exposure on LID development by the 4th year of follow-up.

Salivary α-Synuclein as a Candidate Biomarker of Parkinsonism in 22q11.2 Deletion Syndrome.

Background: 22q11.2 deletion syndrome (22q11.2DS) has been linked to an increased risk of early-onset Parkinson's disease.

A systematic review of salivary biomarkers in Parkinson's disease.

The search for reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis, to detect neurodegeneration from the prodromal phase and to enforce disease-modifying therapies. Despite the need for non-invasively accessible biomarkers, the majority of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers, which require invasive collection procedures. Saliva represents an easily accessible biofluid and an incredibly wide source of molecular biomarkers.

Endoplasmic reticulum stress: A possible connection between intestinal inflammation and neurodegenerative disorders.

Background: Different studies have shown the key role of endoplasmic reticulum (ER) stress in autoimmune and chronic inflammatory disorders, as well as in neurodegenerative diseases. ER stress leads to the formation of misfolded proteins which affect the secretion of different cell types that are crucial for the intestinal homeostasis.

Purpose: In this review, we discuss the role of ER stress and its involvement in the development of inflammatory bowel diseases, chronic conditions that can cause severe damage of the gastrointestinal tract, focusing on the alteration of Paneth cells and goblet cells (the principal secretory phenotypes of the intestinal epithelial cells).

Expression and role of cocaine-amphetamine regulated transcript (CART) in the proliferation of biliary epithelium.

Cholangiocytes, the epithelial cells that line the biliary tree, can proliferate under the stimulation of several factors through both autocrine and paracrine pathways. The cocaine-amphetamine-regulated-transcript (CART) peptide has several physiological functions, and it is widely expressed in several organs. CART increases the survival of hippocampal neurons by upregulating brain-derived neurotrophic factor (BDNF), whose expression has been correlated to the proliferation rate of cholangiocytes.

The Emerging Role of Ferroptosis in Liver Cancers.

Liver cancer represents a global health challenge with worldwide growth. Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Indeed, approximately 90% of HCC cases have a low survival rate.

A Combined Panel of Salivary Biomarkers in de novo Parkinson's Disease.

Objective: To investigate molecular biomarkers of a-synuclein and tau aggregation, autophagy, and inflammation in the saliva of de novo Parkinson's disease (PD) patients in comparison to healthy subjects (HS), and to correlate molecular data with clinical features of PD patients, in order to establish whether abnormalities of these parameters are associated with specific clusters of de novo PD patients, and their potential diagnostic power in differentiating PD patients from HS.

Methods: We measured total and oligomeric a-synuclein, total-tau and phosphorylated-tau, microtubule-associated protein light chain 3 beta (MAP-LC3beta), and tumor necrosis factor alpha (TNFalpha) in the saliva of 80 de novo PD patients and 62 HS, using quantitative enzyme-linked immunosorbent Assay analysis.

Results: Oligomeric a-synuclein, total-tau, MAP-LC3beta, and TNFalpha levels resulted significantly higher in patients with respect to HS, while no significant differences were detected for total a-synuclein or phosphorylated-tau.

Wearable Electrochemical Sensors in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder associated with widespread aggregation of α-synuclein and dopaminergic neuronal loss in the substantia nigra pars compacta. As a result, striatal dopaminergic denervation leads to functional changes in the cortico-basal-ganglia-thalamo-cortical loop, which in turn cause most of the parkinsonian signs and symptoms. Despite tremendous advances in the field in the last two decades, the overall management (i.

Chronic MPTP in Mice Damage-specific Neuronal Phenotypes within Dorsal Laminae of the Spinal Cord.

The neurotoxin 1-methyl, 4-phenyl, 1, 2, 3, 6-tetrahydropiridine (MPTP) is widely used to produce experimental parkinsonism. Such a disease is characterized by neuronal damage in multiple regions beyond the nigrostriatal pathway including the spinal cord. The neurotoxin MPTP damages spinal motor neurons.