Neurochemistry Research Laboratory, Department of Biochemistry, University of Karachi, Karachi, 75270, Pakistan.
Neurobiology Research Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
Mol Biol Rep. 2023 Jun;50(6):4931-4943. doi: 10.1007/s11033-023-08431-3. Epub 2023 Apr 19.
Schizophrenia (SZ) is a complex multifactorial disorder that affects 1% of the population worldwide with no available effective treatment. Although proteomic alterations are reported in SZ however proteomic expression aberrations among different brain regions are not fully determined. Therefore, the present study aimed spatial differential protein expression profiling of three distinct regions of SZ brain and identification of associated affected biological pathways in SZ progression.
Comparative protein expression profiling of three distinct autopsied human brain regions (i.e., substantia nigra, hippocampus and prefrontal cortex) of SZ was performed with respective healthy controls. Using two-dimensional electrophoresis (2DE)-based nano liquid chromatography tandem mass spectrometry (Nano-LC MS /MS) analysis, 1443 proteins were identified out of which 58 connote to be significantly dysregulated, representing 26 of substantia nigra,14 of hippocampus and 18 of prefrontal cortex. The 58 differentially expressed proteins were further analyzed using Ingenuity pathway analysis (IPA). The IPA analysis provided protein-protein interaction networks of several proteins including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kb), extracellular signal regulated kinases 1/2 (ERK1/2), alpha serine / Threonine-protein kinase (AKT1), cellular tumor antigen p53 (TP53) and amyloid precursor protein (APP), holding prime positions in networks and interacts with most of the identified proteins and their closely interacting partners.
These findings provide conceptual insights of novel SZ related pathways and the cross talk of co and contra regulated proteins. This spatial proteomic analysis will further broaden the conceptual framework for schizophrenia research in future.
精神分裂症（SZ）是一种复杂的多因素疾病，全球有 1%的人口受到影响，但目前尚无有效的治疗方法。尽管已有报道称 SZ 存在蛋白质组学改变，但不同脑区的蛋白质组表达异常尚未完全确定。因此，本研究旨在对 SZ 大脑的三个不同区域进行空间差异蛋白质表达谱分析，并确定 SZ 进展过程中相关的受影响生物学途径。
对 SZ 患者和健康对照者的三个不同脑区（即黑质、海马体和前额叶皮层）进行了比较蛋白质表达谱分析。采用二维电泳（2DE）-纳升液相色谱串联质谱（Nano-LC MS/MS）分析，从 1443 种蛋白质中鉴定出 58 种明显失调的蛋白质，其中 26 种来自黑质，14 种来自海马体，18 种来自前额叶皮层。进一步对 58 种差异表达蛋白进行了 Ingenuity 通路分析（IPA）。IPA 分析提供了包括核因子κ轻链增强子的 B 细胞激活因子（NF-kb）、细胞外信号调节激酶 1/2（ERK1/2）、丝氨酸/苏氨酸蛋白激酶（AKT1）、肿瘤蛋白 p53（TP53）和淀粉样前体蛋白（APP）在内的几种蛋白质的蛋白-蛋白相互作用网络，这些蛋白质在网络中处于重要位置，并与大多数鉴定出的蛋白质及其密切相互作用的伙伴相互作用。
这些发现为新型 SZ 相关途径和共同调节及相互拮抗的蛋白质之间的相互作用提供了概念性的见解。这种空间蛋白质组学分析将为未来的精神分裂症研究提供更广泛的概念框架。
