Parkinson's Disease Mechanisms and Treatments

Inhibition of striatal dopamine release by the L-type calcium channel inhibitor isradipine co-varies with risk factors for Parkinson's

Human Endogenous Retrovirus Expression is Dynamically Regulated in Parkinson's Disease

This study identifies up-regulation of human endogenous retrovirus (HERV) transcripts in Parkinson's disease (PD) across multiple tissues and blood, linking TE activation to PD pathogenesis and potential treatment monitoring.

Differential activation states of direct pathway striatal output neurons associated with the development of L-DOPA-induced dyskinesia.

This study identifies differential activation states of D1-MSN subpopulations in response to L-DOPA treatment and links these changes to LID development through activin/TGFβ signaling.

Genome-wide Association Identifies Novel Etiological Insights Associated with Parkinsons Disease in African and African Admixed Populations

Intronic GBA1 variant rs3115534-G, common in African and African admixed ancestry but rare elsewhere, raises Parkinson's disease risk (OR 1.58) and lowers onset age.

Formation of templated inclusions in a forebrain α-synuclein mouse model is independent of LRRK2

This study shows that LRRK2 does not significantly affect the formation of α-synuclein inclusions in the forebrain of mice after PFF injection, but may influence microglial activation.

Age-induced midbrain-striatum assembloids model early phenotypes of Parkinsons disease

This paper introduces midbrain-striatum assembloids with inducible aging to model early Parkinson's disease phenotypes and nigrostriatal connectivity.

G51D mutation of the endogenous rat Snca gene disrupts synaptic localisation of α-synuclein priming for Lewy-like pathology

This study introduces a G51D mutation in the rat Snca gene, leading to synaptic mislocalization of α-synuclein and increased susceptibility to Lewy-like pathology.

Gardenin A improves cognitive and motor function in A53T-α-syn mice

This study evaluates Gardenin A's effects on A53T-α-syn mice, showing improvements in cognitive and motor function and reductions in pathological markers.

Fibrinogen and complement factor H: The two crucial markers of Parkinson's disease with cognitive impairment

This study identifies fibrinogen and complement factor H as potential biomarkers for Parkinson's disease with cognitive impairment by showing they induce motor and cognitive deficits in mice.

Complement C1q-dependent engulfment of alpha-synuclein induces ENS-resident macrophage exhaustion and accelerates Parkinsons-like gut pathology

This study shows that C1q-dependent engulfment of alpha-synuclein by ENS macrophages leads to their exhaustion and worsens Parkinson's-like gut pathology.

Locus coeruleus neuromelanin accumulation and dissipation across the lifespan

This study examines neuromelanin accumulation and dissipation in the locus coeruleus across aging, finding increased intensity until age 60 followed by a decline, with cognitive associations in older adults.

Feed-forward metabotropic signaling by Cav1 Ca2+ channels supports pacemaking in pedunculopontine cholinergic neurons

The paper investigates the role of Cav1.2 Ca2+ channels in pacemaking of PPN cholinergic neurons and their link to oxidative stress and Parkinson's disease vulnerability.

Biomarker discovery in progressive supranuclear palsy from human cerebrospinal fluid using mass spectrometry-based proteomics

The paper identifies potential biomarkers for progressive supranuclear palsy (PSP) in cerebrospinal fluid using proteomics, finding ATP6AP2 as the top performer in distinguishing PSP from Parkinson's Disease and controls.

Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration

This study identifies VGLUT-mediated mechanisms protecting DA neurons from PD-related degeneration, revealing sex-specific effects and transcriptional regulators.

Neuromelanin accumulation drives endogenous synucleinopathy in non-human primates

This study shows that neuromelanin accumulation in non-human primates leads to synucleinopathy and dopaminergic neuron degeneration, mimicking Parkinson's disease pathology.

Reinforcement learning in Parkinson disease is not associated with inflammatory tone

This study investigates the relationship between inflammatory tone and reinforcement learning in Parkinson's disease but finds no significant associations.

Shared GABA transmission pathology in dopamine agonist- and antagonist-induced dyskinesia

This paper identifies shared GABA transmission pathology in L-DOPA-induced and tardive dyskinesia models through structural and functional analysis of striatal neurons.

Autophagic cargo in Lewy bodies: are Lewy bodies a compartment for spatial protein quality control?

The paper investigates whether Lewy bodies form due to impaired autophagy and mitochondrial dysfunction, finding enriched autophagic markers and proteomic evidence of aggresome-like pathways in Lewy bodies.

Neuroimaging and plasma marker evidence for white matter macrostructure loss in Parkinsons disease

The paper shows that white matter macrostructure loss and elevated plasma neurofilament light chain levels are associated with poor outcomes in Parkinson's disease.

Global Parkinson's Genetics Program (GP2) Complex Network Protocol: Defining the causes of sporadic Parkinson's disease

The paper outlines the protocol for integrating genetic and clinical data from a global cohort of over 150,000 participants to study the genetic causes of sporadic Parkinson's disease.

Transcriptomics analyses of the LRRK2 protein interactome reveal distinct molecular signatures for sporadic and LRRK2 Parkinson's Disease

The paper compares transcriptomic changes in LRRK2 protein interactors between sporadic and LRRK2 Parkinson's Disease to identify molecular differences.

Parkinsons Disease Pathology is Directly Correlated to SIRT3 in Human Subjects and Animal Models: Implications for AAV.SIRT3-myc as a Disease-Modifying Therapy.

This paper shows SIRT3 levels decrease with age and in Parkinson's disease, and over-expression of SIRT3 reduces α-synuclein aggregation, supporting AAV.SIRT3-myc as a potential therapy.

UBL3 interaction with α-synuclein is downregulated by silencing MGST3

The paper identifies MGST3 as a key regulator that downregulates the UBL3-α-syn interaction, with oxidative stress also contributing to this effect.

Low-dose inhalation exposure to trichloroethylene induces dopaminergic neurodegeneration in rodents

This study shows that low-dose inhalation of trichloroethylene causes dopaminergic neurodegeneration in rodents, mimicking Parkinson's disease pathology.

New tree shrew Parkinson's model: a cost-effective alternative to monkey models

This paper develops a tree shrew Parkinson's disease model that replicates key clinical and pathological features of PD, offering a cost-effective alternative to primate models.

Genetic meta-analysis of levodopa induced dyskinesia in Parkinson's disease

This paper identifies three novel genetic variants associated with levodopa-induced dyskinesia in Parkinson's disease and confirms associations with ANKK1 and BDNF, while also finding gender, age at onset, and anxiety as risk factors.

Comparing tonic and phasic calcium in the dendrites of vulnerable midbrain neurons

This study compares the role of L-type calcium channels in tonic and phasic calcium dynamics between SNc and PPN neurons, finding distinct contributions to calcium signaling in these cell types.

A viral vector model for circuit-specific synucleinopathy

The paper develops a cell-type specific viral vector mouse model to induce synucleinopathy in individual circuit elements and characterizes its pathological features.

Hippocampal subfield vulnerability to α-synuclein pathology precedes neurodegeneration and cognitive dysfunction

This study shows that α-synuclein fibrils injected into mouse forebrain cause regional pathology, early neuronal degeneration, and cognitive deficits resembling Lewy body diseases.

Developmental exposure to the Parkinson's disease-associated organochlorine pesticide dieldrin alters dopamine neurotransmission in α-synuclein pre-formed fibril (PFF)-injected mice

This study shows that developmental exposure to dieldrin worsens dopamine-related deficits in mice with synucleinopathy, suggesting environmental factors contribute to Parkinson's disease progression.