Dissecting the Relationship Between Neuropsychiatric and Neurodegenerative Disorders

Area of Science:

• Neuroscience
• Pharmacology
• Pathophysiology

Background:

• Neurodegenerative diseases (NDDs) and neuropsychiatric disorders (NPDs) are leading causes of death in the elderly, involving neuronal cell death and behavioral changes.
• NDDs (e.g., Alzheimer's, Parkinson's) cause cognitive decline, while NPDs (e.g., depression, schizophrenia) manifest as behavioral alterations.
• Both NDDs and NPDs share common underlying mechanisms, including post-translational modifications, the microbiota-gut-brain axis, and aberrant signaling pathways.

Purpose of the Study:

• To elucidate the overlapping mechanisms in the pathophysiology of NDDs and NPDs.
• To review therapeutic strategies, including natural compounds, repurposed drugs, and RNA-based interventions, for NDDs and NPDs.
• To highlight the role of the microbiota-gut-brain axis and stress-related signaling in these disorders.

Main Methods:

• Literature review and synthesis of existing research on NDDs and NPDs.
• Analysis of shared molecular mechanisms, including signaling molecules (e.g., pro-inflammatory cytokines, MAPK/ERK) and pathways.
• Examination of therapeutic agents targeting these common pathways.

Main Results:

• NDDs and NPDs share common pathophysiological mechanisms, notably the microbiota-gut-brain axis, cytosol-to-nucleus signaling, and inflammatory processes.
• Key shared molecular players include pro-inflammatory cytokines, γCaMKII, MAPK/ERK, chemokine receptors, and blood-brain barrier (BBB) permeability.
• Alterations in these shared mechanisms are implicated in the development of various NDDs and NPDs.

Conclusions:

• Targeting shared molecular mechanisms and pathways presents a promising therapeutic avenue for both neurodegenerative diseases and neuropsychiatric disorders.
• Natural compounds, repurposed drugs, and RNA interference show potential as therapeutic agents by addressing these common pathophysiological underpinnings.
• Further research into the microbiota-gut-brain axis and stress-related signaling is crucial for developing effective treatments.