Alpha-synuclein Fibrils Inhibit Activation of the BDNF/ERK Signaling Loop in the mPFC to Induce Parkinson's Disease-like Alterations with Depression.

Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats.

Identification and experimental validation of m7G-related molecular subtypes, immune signature, and feature genes in Alzheimer's disease.

Background: Studies has shown that N7-methylguanosine (m7G) modification plays a critical role in neurological diseases. However, the exact role and association of m7G with the immune microenvironment in Alzheimer's disease (AD) remain largely unknown and unexplored.

Methods: The study datasets comprised 667 AD samples and 503 control samples selected from eight datasets in the Gene Expression Omnibus database; m7G regulator genes were obtained from previous literature.

Irisin inhibits microglial senescence via TFAM-mediated mitochondrial metabolism in a mouse model of tauopathy.

Background: The accumulation of senescent microglia has been highlighted as a critical contributor to the progression of tauopathies. Irisin, a muscle-derived hormone produced by the proteolytic cleavage of Fibronectin-domain III containing 5 (FNDC5), mediates the pleiotropic effects of exercise on the physical body. Herein, we investigate the potential role of irisin in microglial senescence in tauopathies.

Analysis and experimental validation of necroptosis-related molecular classification, immune signature and feature genes in Alzheimer's disease.

Necroptosis, a programmed cell death pathway, has been demonstrated to be activated in Alzheimer's disease (AD). However, the precise role of necroptosis and its correlation with immune cell infiltration in AD remains unclear. In this study, we conducted non-negative matrix factorization clustering analysis to identify three subtypes of AD based on necroptosis-relevant genes.

AMPK-mediated autophagy pathway activation promotes ΔFosB degradation to improve levodopa-induced dyskinesia.

Background: Parkinson's disease patients on chronic levodopa often suffer from motor complications, which tend to reduce their quality of life. Levodopa-induced dyskinesia (LID) is one of the most prevalent motor complications, often characterized by abnormal involuntary movements, and the pathogenesis of LID is still unclear but recent studies have suggested the involvement of autophagy.

Methods: The onset of LID was mimicked by chronic levodopa treatment in a unilateral 6-hydroxydopamine (6-OHDA) -lesion rat model.

Identification of metabolism-related subtypes and feature genes in Alzheimer's disease.

Background: Owing to the heterogeneity of Alzheimer's disease (AD), its pathogenic mechanisms are yet to be fully elucidated. Evidence suggests an important role of metabolism in the pathophysiology of AD. Herein, we identified the metabolism-related AD subtypes and feature genes.

Common mechanisms underlying axonal transport deficits in neurodegenerative diseases: a mini review.

Many neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are characterized by the accumulation of pathogenic proteins and abnormal localization of organelles. These pathological features may be related to axonal transport deficits in neurons, which lead to failures in pathological protein targeting to specific sites for degradation and organelle transportation to designated areas needed for normal physiological functioning. Axonal transport deficits are most likely early pathological events in such diseases and gradually lead to the loss of axonal integrity and other degenerative changes.

ONO-2506 Can Delay Levodopa-induced Dyskinesia in the Early Stage.

Background: Levodopa-induced dyskinesia (LID) is a common motor complication of levodopa (L-DOPA) treatment for Parkinson's disease (PD). In recent years, the role of astrocytes in LID has increasingly attracted attention.

Objective: To explore the effect of an astrocyte regulator (ONO-2506) on LID in a rat model and the potential underlying physiological mechanism.