Novel Metal-Free Synthesis of 3-Substituted Isocoumarins and Evaluation of Their Fluorescence Properties for Potential Applications.

A novel metal-free synthesis of 3-substituted isocoumarins through a sequential O-acylation/Wittig reaction has been established. The readily accessible (2-carboxybenzyl)-triphenylphosphonium bromide and diverse chlorides produced various 1-isochromen-1-one in the presence of triethylamine, employing sequential O-acylation and an intramolecular Wittig reaction of acid anhydride. Reactions using these facile conditions have exhibited high functional group tolerance and excellent yields (up to 90%).

Neuroprotection of Exendin-4 by Enhanced Autophagy in a Parkinsonian Rat Model of α-Synucleinopathy.

Glucagon-like peptide-1 (GLP-1) receptor stimulation ameliorates parkinsonian motor and non-motor deficits in both experimental animals and patients; however, the disease-modifying mechanisms of GLP-1 receptor activation have remained unknown. The present study investigated whether exendin-4 (a GLP-1 analogue) can rescue motor deficits and exert disease-modifying effects in a parkinsonian rat model of α-synucleinopathy. This model was established by unilaterally injecting AAV-9-A53T-α-synuclein into the right substantia nigra pars compacta, followed by 4 or 8 weeks of twice-daily intraperitoneal injections of exendin-4 (5 μg/kg/day) starting at 2 weeks after AAV-9-A53T-α-synuclein injections.

LncRNA-T199678 Mitigates α-Synuclein-Induced Dopaminergic Neuron Injury via miR-101-3p.

Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by dopaminergic neuron death and the abnormal accumulation and aggregation of α-synuclein (α-Syn) in the substantia nigra (SN). Although the abnormal accumulation of α-Syn can solely promote and accelerate the progress of PD, the underlying molecular mechanisms remain unknown. Mounting evidence confirms that the abnormal expression of long non-coding RNA (lncRNA) plays an important role in PD.

Alpha-Synuclein Accumulation and Its Phosphorylation in the Enteric Nervous System of Patients Without Neurodegeneration: An Explorative Study.

Alpha-synuclein (α-Syn) is widely distributed and involved in the regulation of the nervous system. The phosphorylation of α-Syn at serine 129 (pα-Syn) is known to be closely associated with α-Synucleinopathies, especially Parkinson's disease (PD). The present study aimed to explore the α-Syn accumulation and its phosphorylation in the enteric nervous system (ENS) in patients without neurodegeneration.

Fasudil Promotes α-Synuclein Clearance in an AAV-Mediated α-Synuclein Rat Model of Parkinson's Disease by Autophagy Activation.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder, but the disease-modifying therapies focusing on the core pathological changes are still unavailable. Rho-associated protein kinase (ROCK) has been suggested as a promising target for developing neuroprotective therapies in PD.

Objective: We aimed to explore the promotion of α-synuclein (α-syn) clearance in a rat model.

Design, synthesis and identification of N, N-dibenzylcinnamamide (DBC) derivatives as novel ligands for α-synuclein fibrils by SPR evaluation system.

PET imaging of α-synuclein (α-syn) deposition in the brain will be an effective tool for earlier diagnosis of Parkinson's disease (PD) due to α-syn aggregation is the widely accepted biomarker for PD. However, the necessary PET radiotracer for imaging is clinically unavailable until now. The lead compound discovery is the first key step for the study.

Depressive Symptoms Are Associated With Color Vision but not Olfactory Function in Patients With Parkinson's Disease.

Depressive symptoms and sensory dysfunction, such as reduction in visual and olfactory function, are common in Parkinson's disease (PD). Previous studies have suggested that depressive symptoms are associated with visual impairments and potentially with hyposmia in several types of mood disorders. However, the relationship between depressive symptoms and sensory dysfunction remains unclear in PD.

Autophagic Modulation by Trehalose Reduces Accumulation of TDP-43 in a Cell Model of Amyotrophic Lateral Sclerosis via TFEB Activation.

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease characterized by the formation of protein inclusion and progressive loss of motor neurons, finally leading to muscle weakness and respiratory failure. So far, the effective drugs for ALS are yet to be developed. Impairment of transcriptional activator transcription factor EB (TFEB) has been demonstrated as a key element in the pathogenesis of ALS.

Evaluation of PDQ-8 and its relationship with PDQ-39 in China: a three-year longitudinal study.

Background: Parkinson's disease is characterized by motor and non-motor symptoms with wide ranging impacts on the health-related quality of life. The 39-item Parkinson's disease Questionnaire (PDQ-39) is the most widely used PD-specific health-related quality-of-life questionnaire. The short-form 8-item Parkinson's disease Questionnaire (PDQ-8) was found to produce results similar to that of the PDQ-39 cross-culturally.

Toward precision medicine in Parkinson's disease.

Precision medicine refers to an innovative approach selected for disease prevention and health promotion according to the individual characteristics of each patient. The goal of precision medicine is to formulate prevention and treatment strategies based on each individual with novel physiological and pathological insights into a certain disease. A multidimensional data-driven approach is about to upgrade "precision medicine" to a higher level of greater individualization in healthcare, a shift towards the treatment of individual patients rather than treating a certain disease including Parkinson's disease (PD).

Cdk5-Dependent Activation of Neuronal Inflammasomes in Parkinson's Disease.

Background: Inflammasomes, which mediate the activation of caspase-1 and maturation of IL-1β and IL-18, have been unambiguously verified to participate in many diseases, such as lung diseases, infectious diseases and Alzheimer's disease, but the relation between Parkinson's disease and inflammasomes is poorly understood.

Methods: The expression, maturation, and secretion of inflammasomes in neurons were measured. The activation of inflammasomes in the substantia nigra of the brain was tested in acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and an α-synuclein transgenic mouse model.

Phosphorylation of Connexin 43 by Cdk5 Modulates Neuronal Migration During Embryonic Brain Development.

The gap junction protein, connexin 43 (Cx43), is only present and abundantly expressed in astrocytes but is absent in neurons in the mature brain tissues. However, both the expression and function of Cx43 in neurons during brain embryonic development remain largely unexplored. In the present study, we confirmed that Cx43 is expressed in the migrating neurons in the embryonic stage of the brain.