Translational Neurodegeneration

Abstract Background Extensive research evidence indicates that neuronal immune receptors play a critical role in Alzheimer's disease (AD). However, it remains unclear how these receptors convert extracellular signals into cellular pathological changes. Proteolytic cleavage of membrane receptors serves as an unconventional pathway for reprogramming cellular functions, and the cleaved fragments oft…

Abstract As the global population ages, neurodegenerative and neuroinflammatory diseases are becoming a rapidly growing public health challenge, with available interventions remaining largely symptomatic and often only modestly affecting long-term disease progression. Therapies involving mesenchymal stromal cells (MSCs) have attracted substantial attention as a potential clinical therapeutic stra…

Abstract Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuron loss and the accumulation of misfolded α-synuclein, yet the underlying mechanisms remain incompletely understood. Over the past two decades, genetic discoveries have highlighted the convergence of multiple familial PD genes on the autophagy-lysosome pathway (ALP), a key cellular syst…

Abstract Background Coenzyme Q10 (CoQ10) is a key mitochondrial electron carrier and a widely used dietary supplement with potential neurological benefits. However, the mechanisms underlying its effect in ameliorating memory deficits caused by cerebellar injury are not fully understood. In this study, we investigated the effects of long-term CoQ10 supplementation on working memory and the underly…

Abstract Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder lacking any proven disease-modifying therapy. Drug repurposing offers a strategy to accelerate the development of treatments by utilizing agents originally approved for other indications. This review summarizes repurposed drugs investigated as disease-modifying therapies for MSA, spanning preclinical in vit…

Alzheimer's disease (AD) is the most prevalent type of dementia, and its pathophysiological mechanisms involve multiple factors, including genomic factors, metabolomic factors, and environmental factors. Lipid dysregulation occurs both centrally and peripherally in patients with AD, and the severity is closely associated with disease progression. Applied studies based on genome-wide association s…

This work provides a detailed characterization of the progressive and multisystem nature of experimental parkinsonism, highlighting the interplay between αSyn pathology, gut-brain signaling, and the onset of non-motor disturbances, with a particular focus on RBD-like alterations in sleep.

Our findings provide mechanistic insights into the reciprocal TRPA1-TLR2 signaling pathway in α-syn-induced astrocyte pathology and underscore the disease-modifying potential of focused transcranial ULIUSm on astrocytes for the treatment of LBD. This study establishes a novel therapeutic strategy to alleviate neuroinflammation and cognitive decline associated with LBD. The demonstration of its lo…

Our findings suggest that SSEA3/CD105 positivity is a potential marker of NTSC therapeutic efficacy for the treatment of AD. Future studies should focus on enhancing the therapeutic potential of SSEA3⁺/CD105⁺ NTSCs by improving their functional efficacy and consistency, and advancing their use in clinical settings.

In conclusion, B. coprocola treatment can improve motor deficits, neuroinflammation, and intestinal function in the rotenone-induced PD mouse model. The effects are associated with microbiota remodeling, regulation of macrophage polarization, and inhibition of the NLRP3 inflammasome pathway. Acetate and butyrate, key metabolites of B. coprocola, might play an important role in promoting M2 macrop…

Mitochondrial DNA (mtDNA) plays a pivotal role in the regulation of neuroinflammation, acting as a potent trigger of innate immune responses when released into the cytoplasm or extracellular space. mtDNA is structurally similar to bacterial DNA, containing unmethylated CpG motifs that are readily recognized by immune sensors. Under conditions of cellular stress, injury, or mitochondrial dysfuncti…

Tauopathies are characterized by aberrant tau structure and function, which is associated with neurodegenerative dementias, such as Alzheimer's disease, Pick's disease, and frontotemporal dementia, as well as the motor neuron disease amyotrophic lateral sclerosis. Consistent association of these neurodegenerative conditions with viruses suggests an interplay between viral activity and the develop…

Alzheimer's disease (AD) is a progressive neurodegenerative disorder driven by multifactorial mechanisms. Increasing evidence suggests that dysbiosis, a term denoting an imbalance in the composition of the microbiota, may play a pivotal role in the pathogenesis of AD across multiple bodily sites, including the gut, oral cavity, nasal passages, lungs, and skin. Microbial imbalances may promote neu…

αSyn pathology propagates along anatomical pathways, but cell-autonomous factors determine if a neuron exposed to misfolded αSyn will develop Lewy-like pathology or not.

The intricate cellular architecture and dynamic molecular interplay in the nervous system have long challenged mechanistic studies of neurological diseases. Conventional approaches often miss the transient, low-affinity, or spatially confined interactions that underlie neural homeostasis and pathogenesis. Proximity labeling (PL) technologies overcome this limitation by enabling in situ capture of…

Advancements in visualization methods have brought the meningeal lymphatic system (MLS) into the spotlight. The meningeal lymphatic vessels (mLVs) play a vital role in draining cerebrospinal fluid and immune cells, acting as a central hub for immune surveillance in the brain. Age-related morphological and functional declines of mLVs suggest their involvement in the pathogenesis of neurodegenerati…

Aging is a multifaceted biological process affecting various organ systems. Immunosenescence, a key feature of aging, markedly increases susceptibility to infections, cancers, autoimmune diseases, and also neurodegenerative disorders. Immunosenescence not only accelerates normal aging but also drives the progression of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's…

Neurodegenerative diseases (NDDs), including Parkinson's disease and Alzheimer's disease, are major age-related disorders characterized by progressive neuronal degeneration and a decline in cognitive and motor functions. Managing NDDs poses an increasing healthcare challenge as the global population ages. The onset of NDDs is linked to protein misfolding, oxidative stress, dysfunction of mitochon…

Variants in the triggering receptor expressed on myeloid cells 2 (TREM2) gene have been demonstrated to increase the risk of late-onset Alzheimer's disease (AD) and Nasu-Hakola disease. As a type I transmembrane receptor, TREM2 is predominantly expressed in microglia within the central nervous system. Extensive research over the past decade has consistently established the critical role of TREM2 …