Publications by authors named "Cheryl Waters"
Article Synopsis
- - Variants in the CTSB gene are linked to an increased risk of Parkinson's disease (PD) and affect the activity of cathepsin B, an enzyme involved in breaking down proteins and regulating cellular processes related to autophagy and lysosome function.
- - CatB can both degrade the harmful alpha-synuclein protein associated with PD and potentially create shorter versions of it that are more prone to aggregation, complicating its role in PD pathology.
- - Experiments showed that inhibiting catB disrupts autophagy and lysosomal function, leading to an accumulation of toxic protein aggregates, while activating catB enhances the clearance of these aggregates in cell and neuron models.
Previous studies have established that rare biallelic SYNJ1 mutations cause autosomal recessive parkinsonism and Parkinson's disease (PD). We analyzed 8165 PD cases, 818 early-onset-PD (EOPD, < 50 years) and 70,363 controls. Burden meta-analysis revealed an association between rare nonsynonymous variants and variants with high Combined Annotation-Dependent Depletion score (> 20) in the Sac1 SYNJ1 domain and PD (Pfdr = 0.
View Article and Find Full Text PDFArticle Synopsis
- Variants in the GBA gene, which codes for glucocerebrosidase (GCase), are major genetic risk factors for Parkinson's disease (PD), leading to decreased GCase activity.
- A genome-wide association study was conducted using two cohorts to identify common variants related to GCase activity, confirming known variants and discovering a new link involving the GAA gene, which encodes for acid alpha-glucosidase.
- The identified associations suggest that other PD-risk loci may also influence GCase activity, indicating a need for further studies to explore these relationships and their functional implications.
Previous studies have suggested that rare biallelic mutations may cause autosomal recessive parkinsonism and Parkinson's disease (PD). Our study explored the impact of rare variants in non-familial settings, including 8,165 PD cases, 818 early-onset PD (EOPD, <50 years) and 70,363 controls. Burden meta-analysis using optimized sequence Kernel association test (SKAT-O) revealed an association between rare nonsynonymous variants in the Sac1 SYNJ1 domain and PD (P=0.
View Article and Find Full Text PDFBackground: Variants in the gene encoding the lysosomal hydrolase cathepsin B (catB) are associated with increased risk of Parkinson's disease (PD). However, neither the specific variants driving these associations nor the functional pathways that link catB to PD pathogenesis have been characterized. CatB activity contributes to lysosomal protein degradation and regulates signaling processes involved in autophagy and lysosome biogenesis.
View Article and Find Full Text PDFParkinson's disease (PD) is the most common neurodegenerative movement disorder, and neuroprotective or disease-modifying interventions remain elusive. High-throughput markers aimed at stratifying patients on the basis of shared etiology are required to ensure the success of disease-modifying therapies in clinical trials. Mitochondrial dysfunction plays a prominent role in the pathogenesis of PD.
View Article and Find Full Text PDFBackground: Several lysosomal genes are associated with Parkinson's disease (PD), yet the association between PD and ARSA remains unclear.
Objectives: To study rare ARSA variants in PD.
Methods: To study rare ARSA variants (minor allele frequency < 0.
Background: Several lysosomal genes are associated with Parkinson's disease (PD), yet the association between PD and , which encodes for the enzyme arylsulfatase A, remains controversial.
Objectives: To evaluate the association between rare variants and PD.
Methods: To study possible association of rare variants (minor allele frequency<0.
Oral levodopa is the most effective treatment for Parkinson disease, but OFF periods emerge over time. Gastrointestinal dysfunction and food effects impact levodopa absorption, contributing to unpredictable control of OFF periods. Inhaled levodopa powder (Inbrija) is approved for on-demand treatment of OFF periods in patients receiving oral levodopa-dopa decarboxylase inhibitors.
View Article and Find Full Text PDFArticle Synopsis
- - The study aimed to create a global cohort of individuals with Parkinson's disease (PD) linked to specific genetic variants, aiming to improve the understanding and treatment of monogenic PD.
- - Researchers collected data from 3,888 participants across 92 centers in 42 countries, including 3,185 diagnosed with PD and 703 unaffected individuals, which highlighted a total of 269 distinct pathogenic variants.
- - This initiative not only established the largest international genetic PD cohort but also provided quality-controlled clinical and genetic data to foster further research collaboration.
The association between glucocerebrosidase, encoded by GBA, and Parkinson's disease (PD) highlights the role of the lysosome in PD pathogenesis. Genome-wide association studies in PD have revealed multiple associated loci, including the GALC locus on chromosome 14. GALC encodes the lysosomal enzyme galactosylceramidase, which plays a pivotal role in the glycosphingolipid metabolism pathway.
View Article and Find Full Text PDFArticle Synopsis
- Recessive mutations in the PRKN, PARK7, and PINK1 genes are known to cause early-onset Parkinson's disease (EOPD), but this study focuses on heterozygous variants instead.
- The research analyzed genetic data from nearly 15,000 Parkinson's cases and over 55,000 controls and found no significant association between these heterozygous variants and Parkinson's disease risk.
- The findings suggest that these variants do not contribute to the risk of developing Parkinson's, indicating a need for larger and more diverse studies to clarify their potential role.
Background: Biallelic mutations in the GBA1 gene encoding glucocerebrosidase cause Gaucher's disease, whereas heterozygous carriers are at risk for Parkinson's disease (PD). Glucosylsphingosine is a clinically meaningful biomarker of Gaucher's disease but could not be assayed previously in heterozygous GBA1 carriers.
Objective: The aim of this study was to assess plasma glucosylsphingosine levels in GBA1 N370S carriers with and without PD.
Article Synopsis
- The study aimed to evaluate whether increasing urate levels through inosine treatment can slow down the progression of early Parkinson's disease, using data that suggests urate elevation might be beneficial.* -
- Conducted as a phase 3 trial, 298 participants with early-stage Parkinson's disease were randomly assigned to receive either inosine to elevate serum urate levels or a placebo, over a period of up to 2 years.* -
- Results from the study indicated no significant differences in clinical progression rates between the inosine and placebo groups, leading to an early closure of the trial based on an interim analysis.*
Background: With the explosion of COVID-19 globally, it was unclear if people with Parkinson's disease (PD) were at increased risk for severe manifestations or negative outcomes.
Objectives: To report on people with PD who had suspected or confirmed COVID-19 to understand how COVID-19 manifested in PD patients.
Methods: We surveyed PD patients who reported COVID-19 to their Movement Disorders specialists at Columbia University Irving Medical Center and respondents from an online survey administered by the Parkinson's Foundation that assessed COVID-19 symptoms, general clinical outcomes and changes in motor and non-motor PD symptoms.
The LRRK2 p.G2019S Parkinson's disease (PD) variant is associated with elevated glucocerebrosidase (GCase) activity in peripheral blood. We aimed to evaluate the association of other LRRK2 variants with PD and its association with GCase activity.
View Article and Find Full Text PDFBackground: Homozygous and compound heterozygous variants in glucocerebrosidase (GBA) can cause Gaucher disease (GD), whereas heterozygous variants increase the risk of developing Parkinson's disease (PD). GD patients display altered peripheral immune proteins. However, it is unknown if these are altered in GBA carriers with PD.
View Article and Find Full Text PDFGenome-wide association studies (GWAS) have identified numerous loci associated with Parkinson's disease. The specific genes and variants that drive the associations within the vast majority of these loci are unknown. We aimed to perform a comprehensive analysis of selected genes to determine the potential role of rare and common genetic variants within these loci.
View Article and Find Full Text PDFRare mutations in genes originally discovered in multigenerational families have been associated with increased risk of Parkinson's disease (PD). The involvement of rare variants in DNAJC13, UCHL1, HTRA2, GIGYF2, and EIF4G1 loci has been poorly studied or has produced conflicting results across cohorts. However, they are still being often referred to as "PD genes" and used in different models.
View Article and Find Full Text PDFIntroduction: CVT-301 (Inbrija®) is a levodopa inhalation powder for on-demand treatment of OFF episodes in Parkinson's disease patients treated with carbidopa/levodopa. Safety and efficacy results of a 12-month, dose-level blinded extension study of a phase 3 trial (SPAN℠-PD) of CVT-301 are presented.
Methods: Patients were receiving oral carbidopa/levodopa and adjunctive CVT-301 treatment, blinded to dose (60 mg or 84 mg, N = 325).
Background: Biallelic PRKN mutation carriers with Parkinson's disease (PD) typically have an earlier disease onset, slow disease progression, and, often, different neuropathology compared to sporadic PD patients. However, the role of heterozygous PRKN variants in the risk of PD is controversial.
Objectives: Our aim was to examine the association between heterozygous PRKN variants, including single-nucleotide variants and copy-number variations (CNVs), and PD.