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Exploring Proteomic Alterations in Intellectual Disability: Insights from Hyperlipidemia and Hyperphosphatasia
Soma Vankwani1, Munazza Raza Mirza2, Muhammad Tahir3
1Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, 75270, Pakistan.
This study reveals distinct molecular pathways in neurodevelopmental disorders (NDDs) associated with intellectual disability (ID), hyperphosphatasia (HPP), and hyperlipidemia (HLD). Findings highlight shared and unique protein disruptions, offering insights into NDD pathophysiology.
Area of Science:
- Biochemistry
- Genetics
- Neuroscience
Background:
- Neurodevelopmental disorders (NDDs) present a complex global health challenge.
- Understanding the multifactorial pathophysiology of NDDs, including intellectual disability (ID), is crucial for early detection and intervention.
- Investigating metabolic comorbidities like hyperphosphatasia (HPP) and hyperlipidemia (HLD) may offer new insights into NDD mechanisms.
Purpose of the Study:
- To investigate the molecular mechanisms underlying NDDs, specifically focusing on the interplay between HPP and HLD in patients with ID.
- To identify distinct and shared proteomic profiles and disturbed biological pathways in ID patients with HPP and HLD compared to healthy controls.
Main Methods:
- Biochemical analysis of blood samples from 800 participants (ID patients and healthy controls).
- Proteomic analysis using nLC-MS/MS on 105 ID patients (ID-HPP and ID-HLD subgroups) and 65 healthy controls.
- Label-free quantitative proteomic analysis to identify differentially expressed proteins and pathway analysis.
Main Results:
- A total of 354 proteins were identified across all groups.
- Distinct protein profiles were observed in ID-HPP (28 differentially expressed proteins) and ID-HLD (85 differentially expressed proteins) groups compared to controls.
- Shared pathways included complement system and lipoprotein metabolism disruptions, while ID-HPP showed distinct toll-like receptor and integrin signaling, and ID-HLD exhibited hemostatic pathway dysregulation.
Conclusions:
- Systemic pathway abnormalities are implicated in NDDs, including ID.
- The study elucidates unique and shared molecular disturbances associated with HPP and HLD in ID patients.
- These findings contribute to a deeper understanding of NDD pathophysiology and potential therapeutic targets.
