Proteomic Profiling of Cerebrospinal Fluid and its Extracellular Vesicles: Insights into Neurological Disorders

George Netto^*
*Correspondence: George Netto, Department of Genetic Biotechnology, Federal University of Uberlândia, Uberlandia, MG 38400-902, Brazil, Email:

Keywords

Cerebrospinal fluid • Vesicles • Diagnosis • Molecular

Introduction

Cerebrospinal Fluid (CSF) is a clear, colorless fluid that surrounds the brain and spinal cord, serving vital functions in maintaining Central Nervous System (CNS) homeostasis. CSF contains a plethora of proteins, peptides, nucleic acids, lipids and other molecules reflective of CNS physiology and pathology. Proteomic profiling of CSF has gained momentum in recent years, offering a comprehensive view of the molecular landscape associated with various neurological disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis and others. Additionally, the study of Extracellular Vesicles (EVs) within CSF has provided new avenues for understanding intercellular communication and disease mechanisms [1].

CSF sampling typically involves lumbar puncture, where a needle is inserted into the subarachnoid space to collect fluid. Careful sample handling and processing are crucial to minimize contamination and degradation of proteins. Various proteomic techniques, including Mass Spectrometry (MS), two-dimensional gel electrophoresis (2D-PAGE) and immunoassays, have been employed for CSF analysis. MS-based approaches, such As Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS), offer high sensitivity and throughput for identifying and quantifying proteins in CSF samples.

Literature Review

Proteomic studies have identified numerous proteins exhibiting differential expression in CSF from patients with neurological disorders compared to healthy controls. These alterations provide insights into disease pathogenesis, potential biomarkers for early diagnosis and therapeutic targets. The identification of specific protein biomarkers in CSF holds promise for improving the diagnosis, prognosis and monitoring of neurological diseases. For instance, the amyloid beta peptide and tau protein levels in CSF are established biomarkers for Alzheimer's disease, aiding in differential diagnosis and disease progression monitoring [2].

Extracellular vesicles are membranous structures released by cells into the extracellular space. EVs in CSF, including exosomes and microvesicles, are derived from CNS cells and carry a cargo of proteins, nucleic acids and lipids. Their biogenesis involves Endosomal Sorting Complexes Required for Transport (ESCRT) machinery or ESCRT-independent pathways. EVs serve as vehicles for intercellular communication within the CNS and between the CNS and peripheral tissues. They facilitate the transfer of biomolecules, including proteins and RNAs, between cells, influencing physiological processes and pathological events. Recent studies have focused on characterizing the proteome of EVs isolated from CSF, revealing a diverse repertoire of proteins implicated in neuronal function, synaptic transmission and disease pathogenesis. Proteomic profiling of CSF EVs holds promise for identifying disease-specific biomarkers and deciphering molecular mechanisms underlying neurological disorders [3].

Discussion

EVs carry proteins associated with AD pathology, such as amyloid beta and tau, offering potential biomarkers for early diagnosis and monitoring disease progression. Moreover, EV-mediated transfer of pathological proteins between neurons may contribute to disease spread. Proteomic analysis of CSF EVs has identified proteins involved in PD pathogenesis, including alpha-synuclein and DJ-1. EV-mediated intercellular communication may play a role in the propagation of alpha-synuclein pathology in PD. CSF EVs from MS patients exhibit altered protein profiles compared to healthy controls, highlighting their potential as biomarkers for disease activity and treatment response. Furthermore, EVs may modulate immune responses and neuroinflammation in MS pathogenesis [4-6].

Conclusion

Proteomic profiling of CSF and its EVs offers valuable insights into the molecular mechanisms underlying neurological disorders. Standardization of CSF collection, processing and EV isolation protocols is essential to ensure reproducibility and comparability of proteomic data across studies. Elucidating the functional roles of proteins identified in CSF and EVs remains a challenge, requiring integrated approaches combining proteomics with other omics technologies and functional assays. Exploiting CSF-derived EVs as delivery vehicles for therapeutic agents, such as small molecules or nucleic acids, holds promise for targeted drug delivery to the CNS. By identifying diseasespecific biomarkers and unraveling intercellular communication networks, these studies contribute to the development of diagnostic tools and therapeutic strategies for improving patient outcomes in neurological diseases.

Acknowledgement

None.

Conflict of Interest

There are no conflicts of interest by author.

References

1. Damodharan, Sudarshawn and Diane Puccetti. "Pediatric central nervous system tumor overview and emerging treatment considerations." Brain Sci 13 (2023): 1106.

   Google Scholar, Crossref, Indexed at

2. Ganz, Jeremy C. "Low grade gliomas." Prog Brain Res 268 (2022): 271-277.

   Google Scholar, Crossref

3. Ryall, Scott, Uri Tabori and Cynthia Hawkins. "Pediatric low-grade glioma in the era of molecular diagnostics." Acta Neuropathol Commun 8 (2020): 1-22.

   Google Scholar, Crossref, Indexed at

4. Salles, Débora, Gabriela Laviola, Andrea Cristina de Moraes Malinverni and João Norberto Stávale. "Pilocytic astrocytoma: A review of general, clinical and molecular characteristics." J Child Neurol 35 (2020): 852-858.

   Google Scholar, Crossref, Indexed at

5. Bauman, Megan MJ, Daniel Jeremiah Harrison, Max B. Giesken and David J. Daniels. "The evolving landscape of pilocytic astrocytoma: A bibliometric analysis of the top-100 most cited publications." Childs Nerv Syst 38 (2022): 1271-1280.

   Google Scholar, Crossref, Indexed at

6. Milde, Till, Fausto J. Rodriguez, Jill S. Barnholtz-Sloan and Nirav Patil, et al. "Reimagining pilocytic astrocytomas in the context of pediatric low-grade gliomas." Neuro Oncol 23 (2021): 1634-1646.

   Google Scholar, Crossref, Indexed at