Alzheimer & Parkinson

Wogonin, a naturally occurring flavonoid derived from Scutellaria species and widely used in traditional East Asian medicine for its anti-inflammatory and antioxidant effects. Although wogonin has demonstrated efficacy against oxidative stress and inflammation, its mechanistic role in Parkinson's disease (PD) remains incompletely understood. The present study investigated the neuroprotective potential of wogonin in a rotenone-induced mice model of PD, with particular emphasis on modulation of...

The integrated stress response (ISR) coordinates cellular adaptation to diverse stress conditions. In Drosophila, two bZIP transcription factors, Xrp1 and crc (ATF4 homolog), are induced during ISR. Crc protein can dimerize with two CEBP factors in vitro, but the in vivo relevance of those interactions remained unknown. Here, we report that the CEBPG homolog, Irbp18, is an essential partner of crc during ISR. Specifically, Irbp18 is broadly required for the transcriptional induction of ISR...

Precision management of Parkinson's disease (PD) requires frequent levodopa (L-dopa) dose adjustments, yet current monitoring relies on subjective symptom reporting and infrequent blood testing. Here, we present a soft, fingertip-mounted wearable platform for continuous, noninvasive L-dopa monitoring. By combining osmotically harvested passive sweat with soft hydrogels, a potentiometric sensing strategy, and individualized calibration, the platform estimates blood L-dopa information from sweat...

Mutations in leucine-rich repeat kinase 2 (LRRK2) are a leading contributor to developing familial and idiopathic Parkinson's disease (PD). Most PD-causing LRRK2 mutations increase the kinase activity, leading to increased phosphorylation of Rab GTPases, disrupting vesicular trafficking, cytoskeletal dynamics, and autophagy. Under homeostatic conditions, the bulk of WT and PD-mutant LRRK2 is found in the cellular cytosol. However, exogenously expressed LRRK2 can form microtubule-associated...

Alzheimer's disease (AD) is the leading cause of dementia, yet current therapies provide limited clinical benefit. Neuroinflammation, as an early and sustained driver of AD, places the NLRP3 inflammasome at the center of pathological and therapeutic focus. In this review, we synthesize recent advances in the structure, assembly, and activation of the NLRP3 inflammasome, and evaluate its contribution to AD using evidence from human brain tissues, cerebrospinal fluid, and diverse AD animal models....

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Fetal tissue transplantation established proof-of-concept for dopamine cell replacement in Parkinson's disease but yielded inconsistent outcomes due to limited tissue availability and cellular heterogeneity. Advances in generating high-purity dopamine progenitors from pluripotent stem cells have enabled standardized products that show safety and motor improvement in clinical trials. However, these trials revealed divergent outcomes arising at three levels: between clinical studies, driven by...

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder lacking effective disease-modifying therapies. Astragalus membranaceus (AM) has shown potential neuroprotective effects, but its underlying mechanisms remain incompletely understood. In this study, a meta-analysis, network pharmacology, molecular simulation, and experimental validation were integrated to investigate the therapeutic potential of AM in AD. Meta-analysis of three randomized controlled trials showed that AM...

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First drug to lower the protein and slow cognitive decline created buzz despite puzzling data.

Alzheimer's disease (AD) disrupts brain function through cell type-specific transcriptomic and epigenomic alterations, yet the contribution of three-dimensional (3D) genome organization to AD remains poorly understood. We applied GAGE-seq (genome architecture and gene expression by sequencing) to jointly profile gene expression and 3D chromatin structure in single cells from postmortem brain tissue from AD patients and age-matched individuals without AD, revealing chromatin reorganization linked...

Targeted protein degradation (TPD) via proteolysis-targeting chimeras (PROTACs) offers a promising strategy for modulating disease-associated proteins, yet effective brain-preferred protein degradation remains challenging. Herein, we report a dual-function PROTAC, dACSL4, and its nose-to-brain delivery for brain-preferred protein degradation and therapeutic suppression of ferroptosis in neurodegeneration. dACSL4 selectively degrades acyl-CoA synthetase long-chain family member 4 (ACSL4) while...

Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta, but the molecular events preceding neuronal loss remain unclear. Here, we combine spatial transcriptomics, spatial proteomics, and α-synuclein (αSyn) seed amplification assays to profile post-mortem midbrain tissue from controls, incidental Lewy body disease (iLBD), PD, Alzheimer's disease (AD), and AD with Lewy body pathology (AD + LBP). We find that αSyn seeding activity...

Early-life nutrition is linked to adult brain health, yet evidence from quasi-experimental studies remains scarce. Leveraging the UK's historical sugar rationing as a natural experiment, we examined whether early-life sugar restriction reduces the risk of neurodegenerative and psychiatric disorders in later life. Among 60,394 UK Biobank participants (born 1951-1956), three groups were defined: in-utero-only, in utero plus 2 years, and non-rationed controls. Compared with non-rationed...

CONCLUSIONS: In summary, the different brain aging patterns, each based around specific underlying circuits, may serve as neuroimaging biomarkers for understanding the neural aging mechanisms in commonly occurring brain disorders. Future studies should test whether these disorder-specific brain aging patterns can serve as useful biomarkers to guide critical clinical decision-making.

Parkinsonism is a common clinical manifestation of Parkinson's disease (PD) and other atypical parkinsonism (AP). Diffusion tensor imaging (DTI) may help characterize pathological alterations in cerebral white matter (WM). This study aimed to analyze the differences in early white matter microstructural alterations between PD and AP using DTI and to explore the potential value of DTI in the early differential diagnosis of PD and AP. DTI data were acquired from 12 patients with early PD, 11 with...

Blood-based biomarkers are emerging as scalable tools for the diagnosis and monitoring of neurodegenerative diseases, but markers enabling differential diagnosis across major dementias remain limited. Here we show that large-scale plasma proteomics identifies disease-associated signatures across Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia. We analyzed 1,318 plasma samples from well-characterized international cohorts and identified more than 200 dysregulated...

Aging is characterized by progressive loss of proteostasis, and heat shock transcription factor 1 (HSF1) is the master regulator of the cellular stress response, making it an attractive pharmacological target for interventions aimed at extending lifespan. However, a systematic synthesis of phytochemicals that modulate HSF1 has been lacking. Following PRISMA 2020 guidelines, we systematically searched PubMed, Web of Science, Scopus, Embase, and the Cochrane Library from March 2016 to March 2026,...

Alzheimer's disease (AD) is a common age-related neurodegenerative disorder (NDD), with ageing as its primary risk factor. Cellular senescence, characterized by permanent cell-cycle arrest, apoptosis resistance and acquisition of the senescence-associated secretory phenotype (SASP), is the cellular hallmark of ageing. Recent evidence indicates that blood-brain barrier (BBB) dysfunction precedes cognitive decline and pathological protein deposition, representing an early event in AD, with the...

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. It is associated with the ongoing degeneration of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies that contain α-synuclein. These pathological changes lead to abnormalities of motor symptoms (tremor, rigidity, bradykinesia) and non-motor symptoms (cognitive decline, sleep abnormalities, psychiatric abnormalities). The pathogenesis of PD is complex and multifactorial,...