Parkinson's Disease Mechanisms and Treatments

This paper integrates eQTL and Parkinson’s disease GWAS data to identify 11 disease genes and pathways involved in PD risk through colocalisation, TWAS, and network analysis.

This study shows that knocking down GPR88 in the associative striatum of a rat PD model reduces psychiatric symptoms by modulating Rgs4 and ΔFosB.

The paper simulates alpha-synuclein spread using a connectome model and finds connectivity alone is insufficient to explain observed pathology patterns in rats.

This study identifies two genome-wide significant variants associated with Parkinson's disease progression and replicates known risk variants' effects on motor and cognitive decline.

This study identifies pathology-inducing α-synuclein species in human brain tissue and shows that C-terminal antibodies can immunodeplete them.

This study identifies Rab10 as a critical mediator of LRRK2-G2019S-induced neurodegeneration in specific dopaminergic neurons, showing rescue of visual and motor deficits but not sleep dysfunction.

This study identifies HDAC6 as a novel LRRK2 substrate and shows that LRRK2-mediated phosphorylation of HDAC6 enhances aggresome formation, linking LRRK2 dysfunction to Parkinson's disease pathology.

This study uses non-motor features and genetic variants to cluster Lewy body diseases, identifying distinct patient groups with different clinical and cognitive profiles.

The paper shows that BT13, a GDNF receptor agonist, supports dopamine neuron survival in vitro and protects their function in a Parkinson's disease rat model by crossing the blood-brain barrier.

This study uses PMCA to show that alpha-synuclein aggregates from mutant mice can seed aggregation in wild-type mice and other substrates, mimicking prion-like behavior.

This study shows that misfolded α-synuclein spreads from urogenital nerves to the brain, causing MSA-like symptoms through micturition reflex pathways.

This paper identifies a brain atrophy pattern from MRI that predicts disease progression in early Parkinson's disease better than other biomarkers.

The paper examines crystalline particles in Parkinson's disease substantia nigra using TEM, identifying calcium oxalate and TiO2 as potential contributors to dopaminergic neuron death through inflammasome activation.

This paper validates the 2017 MDS-PSP criteria for diagnosing PSP and variant syndromes using neuropathological data, showing higher sensitivity but lower specificity compared to older criteria.

Calpain-1/2 cleavage of the alpha-synuclein C-terminus after fibril formation is reported to drive seeding, aggregation and the maturation of Lewy-body-like inclusions in primary neurons.

This study shows that chronic corticosterone worsens alpha-synuclein pathology and neurodegeneration in a mouse model of Parkinson's disease.

This study shows HtrA2/Omi specifically degrades oligomeric α-synuclein to protect against neurodegeneration in Parkinson's disease models.

This study applies a seed-inference algorithm to Parkinson's Disease patients to show that atrophy patterns vary significantly between individuals and are better predicted by individualized seed locations than standard regions.

This study shows that Parkinson's disease-linked Parkin mutations impair glutamatergic synaptic transmission and plasticity by disrupting NMDA and AMPA receptor trafficking.

This study identifies ROCK1-regulated mitochondrial fission as a key mechanism in dopaminergic nerve cell apoptosis in Parkinson's disease.

This study uses machine learning to identify Parkinson disease subtypes and predict progression, finding three distinct subtypes with accurate progression predictions.

This study uses metabolomics to identify metabolic differences between Parkinson’s disease and control patients, highlighting the impact of levodopa on observed variations.

The paper uses molecular dynamics simulations to show that mutant α-synuclein amyloids have switchable β-sheet structures that may explain their strain-like properties.

This study identifies increased autofluorescence in fingernails and skin as a potential diagnostic biomarker for Parkinson's disease, distinguishing it from healthy individuals and acute ischemic stroke patients.

This study shows that reduced SYNJ1 expression with age contributes to dopamine neuron vulnerability and Parkinson's disease pathogenesis in mice.

This study uses fMRI to examine how trait impulsivity relates to response-inhibition performance and brain activation in Parkinson's disease patients.

This study shows that increased tyrosine hydroxylase activity in mice leads to higher dopamine levels, amphetamine response, and oxidative stress markers, suggesting a potential mechanism for neurodegeneration in Parkinson's disease.

The paper re-evaluates TMEM230 mutations in familial Parkinson’s disease using updated genetic data and experiments, confirming TMEM230 as a PD-causing gene.

The paper identifies β-synuclein on secretory granules in chromaffin cells and shows that α-synuclein accelerates BDNF discharge by speeding fusion pore expansion.