Cathepsins and neurological diseases: a Mendelian randomization study

Area of Science:

• Neuroscience
• Genetics
• Biochemistry

Background:

• The link between cathepsins and neurological diseases is not well understood.
• Cathepsins are enzymes involved in protein degradation.
• Neurological diseases encompass a range of debilitating conditions affecting the brain and nervous system.

Purpose of the Study:

• To investigate the potential causal relationships between cathepsins and various neurological diseases.
• To utilize a robust two-sample Mendelian randomization (MR) approach for causal inference.
• To identify specific cathepsins associated with increased or decreased risk of neurological conditions.

Main Methods:

• A two-sample, two-way Mendelian randomization (MR) study was performed.
• Data from genome-wide association studies (GWAS) for 10 cathepsins and 7 neurological diseases were pooled.
• Statistical methods included inverse variance weighting (IVW), weighted median, MR Egger regression, and sensitivity analyses.

Main Results:

• Cathepsin B and D showed a causal association with Parkinson's disease.
• Cathepsin E and O were causally linked to ischemic stroke.
• A reverse causal association was observed between multiple sclerosis and Cathepsin E.

Conclusions:

• Cathepsins B, D, E, and O are causally implicated in the development of specific neurological diseases.
• These findings provide valuable insights for the diagnosis and treatment of neurological disorders.
• Further research is warranted to explore the precise mechanisms underlying these associations.