Different charged biopolymers induce α-synuclein to form fibrils with distinct structures.

The aggregation of α-synuclein (α-syn) into amyloid fibrils, a key process in the development of Parkinson's disease (PD) and other synucleinopathies, is influenced by a range of factors such as charged biopolymers, chaperones, and metabolites. However, the specific impacts of different biopolymers on α-syn fibril structure are not well understood. In our work, we found that different polyanions and polycations, such as polyphosphate (polyP), polyuridine (polyU), and polyamines (including putrescine, spermidine, and spermine), markedly altered the fibrillation kinetics of α-syn in vitro.

CircRNA and Stroke: New Insight of Potential Biomarkers and Therapeutic Targets.

Stroke, the second-largest cause of death and the leading cause of disability globally, presents significant challenges in terms of prognosis and treatment. Identifying reliable prognosis biomarkers and treatment targets is crucial to address these challenges. Circular RNA (circRNA) has emerged as a promising research biomarkers and therapeutic targets because of its tissue specificity and conservation.

The impacts of health insurance and resource on the burden of Alzheimer's disease and related dementias in the world population.

Introduction: The increasing prevalence of Alzheimer's disease and related dementias (ADRD) presents both a burden and an opportunity for intervention. This study aims to estimate the impacts of health insurance and resources on the burden attributed to ADRD.

Method: Data were mainly collected from global databases for ADRD.

The neuroprotective effects of oxygen therapy in Alzheimer's disease: a narrative review.

Alzheimer's disease (AD) is a degenerative neurological disease that primarily affects the elderly. Drug therapy is the main strategy for AD treatment, but current treatments suffer from poor efficacy and a number of side effects. Non-drug therapy is attracting more attention and may be a better strategy for treatment of AD.

Association Between Plasma Apolipoprotein M With Alzheimer's Disease: A Cross-Sectional Pilot Study From China.

Background: Recent evidence of genetics and metabonomics indicated a potential role of apolipoprotein M (ApoM) in the pathogenesis of Alzheimer's disease (AD). Here, we aimed to investigate the association between plasma ApoM with AD.

Methods: A multicenter, cross-sectional study recruited patients with AD ( = 67), age- and sex-matched cognitively normal (CN) controls ( = 73).

Neuroprotective effects of naturally sourced bioactive polysaccharides: an update.

Polysaccharides are macromolecular complexes that have various biological activities. In vivo and in vitro studies have shown that polysaccharides play neuroprotective roles through multiple mechanisms; consequently, they have potential in the prevention and treatment of neurodegenerative diseases. This paper summarizes related research published during 2015-2020 and reviews advances in the understanding of the neuroprotective effects of bioactive polysaccharides.

Association Between Serum C1q Tumor Necrosis Factor-Related Protein 9 and the Clinical Characteristics and Prognosis of Ischemic Stroke.

Introduction: C1q tumor necrosis factor (TNF)-related protein 9 (CTRP9) is a novel member of the C1q/TNF superfamily. According to our previous review, CTRP9 plays a vital role in the process of cardiovascular diseases, including regulating energy metabolism, modulating vasomotion, protecting endothelial cells, inhibiting platelet activation, inhibiting pathological vascular remodeling, stabilizing atherosclerotic plaques, and protecting the heart. We proposed that CTRP9 could play multiple positive and beneficial roles in vascular lesions in ischemic stroke (IS).

Current Alzheimer disease research highlights: evidence for novel risk factors.

Alzheimer disease (AD) is the most common type of dementia characterized by the progressive cognitive and social decline. Clinical drug targets have heavily focused on the amyloid hypothesis, with amyloid beta (Aβ), and tau proteins as key pathophysiologic markers of AD. However, no effective treatment has been developed so far, which prompts researchers to focus on other aspects of AD beyond Aβ, and tau proteins.

New therapeutics beyond amyloid-β and tau for the treatment of Alzheimer's disease.

As the population ages, Alzheimer's disease (AD), the most common neurodegenerative disease in elderly people, will impose social and economic burdens to the world. Currently approved drugs for the treatment of AD including cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and an N-methyl-D-aspartic acid receptor antagonist (memantine) are symptomatic but poorly affect the progression of the disease. In recent decades, the concept of amyloid-β (Aβ) cascade and tau hyperphosphorylation leading to AD has dominated AD drug development.

Autophagy and Ubiquitin-Proteasome System.

Millions of protein molecules are synthesized per minute in each cell, and simultaneously, millions of protein molecules are degraded. Mutated and misfolded newly synthesized proteins are rapidly degraded to prevent the toxicity caused by the accumulation of these protein fragments. There are two main mechanisms of intracellular protein degradation: the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway (ALP).

The Role of Nanomaterials in Autophagy.

With the development of nanotechnology and the emergence of new nanomaterials, the effect of nanomaterials on autophagy regulation has attracted increasing attention. Nanomaterial-mediated autophagy regulation has potential applications in the diagnosis and treatment of autophagy-related diseases, such as cancer treatment, drug sensitization and neurodegenerative diseases. Different nanomaterials can regulate autophagy through different mechanisms because of their unique physical, chemical and biological properties.

Therapeutic effects of hirsutella sinensis on the disease onset and progression of amyotrophic lateral sclerosis in SOD1 transgenic mouse model.

Aims: Although the pathophysiology of amyotrophic lateral sclerosis (ALS) is still not completely understood, the deregulated microglia polarization and neuroinflammation have been shown to contribute to the pathogenesis and progression of this disease. In the present study, we aimed to determine whether hirsutella sinensis (HS) could reduce neuroinflammatory and pathological changes in the spinal cord of SOD1 model mice of ALS and consequently ameliorate disease onset and progression.

Methods: SOD1 mice were chronically treated with HS by gavage.

Repurposing carbamazepine for the treatment of amyotrophic lateral sclerosis in SOD1-G93A mouse model.

Aims: To investigate the effect and mechanisms of carbamazepine (CBZ) on the onset and progression of amyotrophic lateral sclerosis (ALS) in SOD1-G93A mouse model.

Methods: Starting from 64 days of age, SOD1-G93A mice were orally administered with CBZ at 200 mg/kg once daily until death. The disease onset and life span of SOD1-G93A mice were recorded.

Restless legs syndrome secondary to pontine infarction: Clinical analysis of five cases.

Objective: Pontine infarction is a common type of stroke in the cerebral deep structures, resulting from occlusion of small penetrating arteries, may manifest as hemi-paralysis, hemi-sensory deficit, ataxia, vertigo, and bulbar dysfunction, but patients presenting with restless legs syndrome (RLS) are extremely rare. Herein, we reported five cases with RLS as a major manifestation of pontine infarction.

Methods: Five cases of pontine infarction related RLS were collected from July 2013 to February 2016.

Activation of DRD5 (dopamine receptor D5) inhibits tumor growth by autophagic cell death.

Dopamine agonists such as bromocriptine and cabergoline have been successfully used in the treatment of pituitary prolactinomas and other neuroendocrine tumors. However, their therapeutic mechanisms are not fully understood. In this study we demonstrated that DRD5 (dopamine receptor D5) agonists were potent inhibitors of pituitary tumor growth.

n-butylidenephthalide treatment prolongs life span and attenuates motor neuron loss in SOD1 mouse model of amyotrophic lateral sclerosis.

Aims: To evaluate the therapeutic effects of n-butylidenephthalide (BP) in SOD1 mouse model of amyotrophic lateral sclerosis and explore the possible mechanisms.

Methods: The SOD1 mice were treated by oral administration of BP (q.d.

Nurr1-Based Therapies for Parkinson's Disease.

Previous studies have documented that orphan nuclear receptor Nurr1 (also known as NR4A2) plays important roles in the midbrain dopamine (DA) neuron development, differentiation, and survival. Furthermore, it has been reported that the defects in Nurr1 are associated with Parkinson's disease (PD). Thus, Nurr1 might be a potential therapeutic target for PD.

Current Therapy of Drugs in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS), commonly termed as motor neuron disease (MND) in UK, is a chronically lethal disorder among the neurodegenerative diseases, meanwhile. ALS is basically irreversible and progressive deterioration of upper and lower motor neurons in the motor cortex, brain stem and medulla spinalis. Riluzole, used for the treatment of ALS, was demonstrated to slightly delay the initiation of respiratory dysfunction and extend the median survival of patients by a few months.

Suppression of mTOR pathway and induction of autophagy-dependent cell death by cabergoline.

Cabergoline (CAB), the first-line drug for treatment of prolactinomas, is effective in suppressing prolactin hypersecretion, reducing tumor size, and restoring gonadal function. However, mechanisms for CAB-mediated tumor shrinkage are largely unknown. Here we report a novel cytotoxic mechanism for CAB.

Double-Edged Roles of Nitric Oxide Signaling on APP Processing and Amyloid-β Production In Vitro: Preliminary Evidence from Sodium Nitroprusside.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is thought to be caused in part by the age-related accumulation of amyloid-β (Aβ) in the brain. Recent findings have revealed that nitric oxide (NO) modulates the processing of amyloid-β precursor protein (APP) and alters Aβ production; however, the previously presented data are contradictory and the underlying molecular mechanisms are still incomplete. Here, using human SH-SY5Y neuroblastoma cells stably transfected with wild-type APPwt695, we found that NO, derived from NO donor sodium nitroprusside (SNP), bi-directionally modulates APP processing in vitro.

A New VMAT-2 Inhibitor NBI-641449 in the Treatment of Huntington Disease.

Aims: To evaluate the effectiveness of a new VMAT-2 inhibitor NBI-641449 in controlling hyperkinetic movements of Huntington disease (HD) and to investigate its possible therapeutic effects.

Methods: We applied three different doses of NBI-641449 (1, 10, 100 mg/kg/day) for 2 weeks in 4-month-old YAC128 mice and wild-type (WT) mice. Rotarod performance and locomotive activities were tested during the administration of the drug.

Progress in Diagnosing Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes.

Objective: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a progressive, multisystem affected mitochondrial disease associated with a number of disease-related defective genes. MELAS has unpredictable presentations and clinical course, and it can be commonly misdiagnosed as encephalitis, cerebral infarction, or brain neoplasms. This review aimed to update the diagnosis progress in MELAS, which may provide better understanding of the disease nature and help make the right diagnosis as well.

Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease.

Background: Nurr1 plays an essential role in the development, survival, and function maintenance of midbrain dopaminergic (DA) neurons, and it is a potential target for Parkinson's disease (PD). Nurr1 mRNA can be detected in peripheral blood mononuclear cells (PBMCs), but whether there is any association of altered Nurr1 expression in PBMC with the disease and DA drug treatments remains elusive. This study aimed to measure the Nurr1 mRNA level in PBMC and evaluate the effect of Nurr1 expression by DA agents in vivo and in vitro.