This study identifies a previously unrecognized dopaminergic projection from the locus coeruleus to the retrosplenial cortex that controls short-term declarative memory and is functionally compromised in Parkinson's model mice, with optogenetic and chemogenetic manipulations demonstrating causal…

In an acute MPTP mouse model, 14-day intraperitoneal chrysoeriol (5 mg/kg) treatment improved motor and cognitive behaviors, reduced neuronal damage and alpha-synuclein levels, improved the Bcl-2/Bax ratio, and implicated PI3K/Akt-mediated mitochondrial protection.

Computational network pharmacology, docking, and 100-ns molecular dynamics indicate methoxylated flavonoids—notably Eupatilin—bind multiple PD-relevant targets (HSP90AA1, MMP9, GSK-3β, AKT1) and modulate PI3K-Akt signaling with favorable predicted ADMET.

This review synthesizes evidence that astrocytes and microglia actively shape dopaminergic signaling, neuroinflammation, metabolism, and behavior and proposes a translational framework to target glial states to restore dopamine homeostasis in disorders including Parkinson's disease.

This study shows that upregulated FICD-mediated AMPylation in dopaminergic neurons drives lysosomal dysfunction, ER stress, reduced protein turnover and α-synuclein aggregation across human post-mortem tissue, patient iPSC-derived neurons, and synucleinopathy models, and that pharmacological…

GBA1 mutations drive upregulation of LCN2 across multiple in vivo and in vitro models, and LCN2 promotes α-synuclein accumulation, oxidative stress, and dopaminergic neuron loss while genetic deletion or antibody intervention mitigates these effects.

This study identifies biallelic PSMF1 (hPI31) variants causing a spectrum from early-onset parkinsonism to perinatal lethality, links these variants to altered proteasome assembly and mitochondrial dysfunction in patient cells, and shows age-dependent motor deficits and dopaminergic…

In MPTP-treated mice and astrocyte cultures, inhibition of S100A9 with paquinimod reversed senescence markers, reduced SASP factors, restored mitochondrial biogenesis gene expression and TH-positive fibers, and improved motor behavior, while recombinant S100A9 induced senescence-like and…

Using DAT-SPECT and the SuStaIn algorithm in 636 drug‑naive PD patients, the study identifies three reproducible nigrostriatal degeneration subtypes with distinct clinical features, CSF α‑synuclein seeding associations, and differential longitudinal treatment responses.

In a 6-OHDA rat model of levodopa-induced dyskinesia, striatal ATG14 overexpression enhanced SNARE-dependent autophagosome-lysosome fusion, promoted ΔFosB degradation, and reduced dyskinesia, effects that were blocked by the autophagy inhibitor chloroquine.

Integrative analysis of substantia nigra transcriptomes from 22 PD and 22 controls across three GEO datasets identified 85 consensus differentially expressed mRNAs—including molecular chaperones (DNAJB1, HSPA1B/L), dopaminergic markers (TH, SLC6A3), ECM components—and 20 PPI hub genes, with…

This in vitro study shows resveratrol-loaded polymeric nanoparticles protect PC12 cells and astrocytes from rotenone-induced oxidative stress, mitochondrial dysfunction, and apoptosis while modulating NRF2/HMOX-1 expression.

In a paraquat+lectin rat 'body-first' PD model, 60 days of twice-daily levodopa/benserazide administered after established motor deficits produced no long-term changes in motor or visuospatial memory performance, nigral dopaminergic or medial septal cholinergic neuron loss, or phosphorylated…

Multimodal PET study in 33 PD patients and 25 controls found expected striatal dopaminergic deficits and regional serotonergic reductions but no group differences or longitudinal change in synaptic density (11C‑UCB‑J), with limited clinical correlations.

Wearable gyro sensors during forearm rotation (but not finger tapping) revealed greater upper-limb motor asymmetry in early, drug‑naïve PD versus SWEDD, with asymmetry indices correlating with clinical motor scores.

Integrative single-nucleus RNA-seq across multiple neurodegenerative diseases defines a conserved inflammatory microglial transcriptional program and nominates SPP1 (osteopontin) as a conserved disease-associated microglial biomarker validated in mouse models.

A review evaluating nanoengineered delivery systems (lipid, polymeric, vesicular, dendritic) to enhance brain bioavailability and therapeutic efficacy of plant-derived neuroprotective phytochemicals, integrating mechanistic rationale, preclinical/early clinical evidence, and translational…

The paper describes synthesis, in vitro screening, and molecular modeling of 2‑aroylbenzothiophene analogues that are selective hMAO‑B inhibitors (notably compounds 4, 11, 12) and show modest neuroprotection in SH‑SY5Y cells versus 6‑OHDA, but exhibit cytotoxicity/ROS generation at high micromolar…

This review argues that a "body-first" subtype of Parkinson's may begin in the GI tract—driven by environmental insults, α-synuclein misfolding, oxidative stress and enteric glial activation—that propagates retrogradely via the vagus to the brain and discusses implications for early gut-targeted…

This review advocates integrating peptidomics—high-resolution LC-MS/MS workflows and AI-driven peptide identification—into microbiome research to capture unstable host and microbial signaling peptides and proteolytic fragments that are missed by genomics/proteomics, with implications for biomarkers…

This review summarizes current knowledge on mitochondria-associated membranes (MAMs)/ER–mitochondria contacts, their roles in calcium signaling, ROS, autophagy, inflammation and lipid metabolism, and discusses how MAM dysfunction contributes to aging and age-related neurodegenerative diseases…

The paper shows that forming a silver(I) trimeric complex with Anle138b alters α-synuclein aggregation in PFF-treated cell cultures by selectively reducing a ~12.4 kDa C-terminal truncated α-synuclein species and increasing aggregate size/morphology relative to the parent compound.

rAAV-mediated re-expression of Fbxo7 in a conditional Fbxo7 knockout mouse prevents and reverses progressive loss of nigrostriatal dopaminergic terminals, restoring TH and DAT immunoreactivity even after phenotype onset.

Recent clinical work indicates that dopaminergic progenitor cells derived from iPSCs or hESCs achieve graft survival and favorable safety with apparent absence of graft‑induced dyskinesia, though definitive clinical efficacy remains to be established in well‑designed trials.

The authors report synthesis of chiral Co/Zn Schiff-base clusters (R/S-Co4Zn5L10 and related Co complexes) and show that R-enantiomers rescue dopaminergic neuron loss, improve dopamine-dependent locomotion, and inhibit α-synuclein aggregation in nematode Parkinson’s models.