Exp Neurobiol.
2019 Jun;28(3):362-375. 10.5607/en.2019.28.3.362.
Quantitative Proteomic Analysis Reveals Impaired Axonal Guidance Signaling in Human Postmortem Brain Tissues of Chronic Traumatic Encephalopathy
- Affiliations
-
- 1Departments of Neurology, Pathology, and Surgery, Boston University School of Medicine, Boston, MA 02118, USA. amckee@bu.edu, jyang@bu.edu, hoonryu@bu.edu
- 2Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China.
- 3Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan 250012, China.
- 4Proteomics Laboratory, VA Boston Healthcare System, Boston, MA 02130, USA.
- 5Center for Neuromedicine, Brain Science Institute, Korea Institute of Science and Technology, Seoul 04535, Korea.
- 6Boston University Alzheimer's Disease Center (BU ADC) and Chronic Traumatic Encephalopathy (CTE) Center, Boston University School of Medicine, Boston, MA 02118, USA.
- KMID: 2451072
- DOI: http://doi.org/10.5607/en.2019.28.3.362
Abstract
- Chronic traumatic encephalopathy (CTE) is a distinct neurodegenerative disease that associated with repetitive head trauma. CTE is neuropathologically defined by the perivascular accumulation of abnormally phosphorylated tau protein in the depths of the sulci in the cerebral cortices. In advanced CTE, hyperphosphorylated tau protein deposits are found in widespread regions of brain, however the mechanisms of the progressive neurodegeneration in CTE are not fully understood. In order to identify which proteomic signatures are associated with CTE, we prepared RIPA-soluble fractions and performed quantitative proteomic analysis of postmortem brain tissue from individuals neuropathologically diagnosed with CTE. We found that axonal guidance signaling pathwayrelated proteins were most significantly decreased in CTE. Immunohistochemistry and Western blot analysis showed that axonal signaling pathway-related proteins were down regulated in neurons and oligodendrocytes and neuron-specific cytoskeletal proteins such as TUBB3 and CFL1 were reduced in the neuropils and cell body in CTE. Moreover, oligodendrocyte-specific proteins such as MAG and TUBB4 were decreased in the neuropils in both gray matter and white matter in CTE, which correlated with the degree of axonal injury and degeneration. Our findings indicate that deregulation of axonal guidance proteins in neurons and oligodendrocytes is associated with the neuropathology in CTE. Together, altered axonal guidance proteins may be potential pathological markers for CTE.
Keyword
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Diagnostic History of Traumatic Axonal Injury in Patients with Cerebral Concussion and Mild Traumatic Brain Injury
- A Case of Wernicke's Encephalopathy Presenting as Acute Bilateral Wrist Drop
- Analysis of Diffuse Axonal Injury Using Diffusion Tensor Imaging in Traumatic Brain Injury Patients
- Single Versus Repetitive Traumatic Brain Injury: Current Knowledge on the Chronic Outcomes, Neuropathology and the Role of TDP-43 Proteinopathy
- Central Pain Due to Traumatic Axonal Injury of the Spinothalamic Tract in Patients with Mild Traumatic Brain Injury
