Studying the role of neuron-glial interactions in the production of truncated tau: relevance to Alzheimer's disease

Gómez Sacristán, Pablo (2019). Studying the role of neuron-glial interactions in the production of truncated tau: relevance to Alzheimer's disease. Proyecto Fin de Carrera / Trabajo Fin de Grado, E.T.S. de Ingeniería Agronómica, Alimentaria y de Biosistemas (UPM), Madrid.

Description

Title: Studying the role of neuron-glial interactions in the production of truncated tau: relevance to Alzheimer's disease
Author/s:
  • Gómez Sacristán, Pablo
Contributor/s:
  • Boland, Barry
  • Oñate Sanchez, Luis
Item Type: Final Project
Degree: Grado en Biotecnología
Date: July 2019
Subjects:
Faculty: E.T.S. de Ingeniería Agronómica, Alimentaria y de Biosistemas (UPM)
Department: Biotecnología - Biología Vegetal
Creative Commons Licenses: Recognition - No derivative works - Non commercial

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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that is caused by the degeneration of areas in the brain such as the hippocampus and cortex. It is the most common type of dementia and the number of people affected is rising. AD is characterized by the presence of protein aggregates: amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), which are composed by tau protein. Tau is a microtubule-associated binding protein that is found predominantly in neurons and its function is to keep axonal integrity. In AD, tau undergoes abnormal modifications such as truncation, that lead to the formation of NFTs. The accumulation and spread of these aggregates are defined as Braak stages and correlates with clinical severity of AD. Previous experiments in Dr. Boland's lab showed that a truncated form of tau of approximately 36 kDa was produced in the brain at early stages of AD (Braak stage II). After a screening of compounds on rat cortical neuron models, it was observed that 36 kDa truncated tau was produced when cultures were treated with zinc and glutamate and decreased with kynurenic acid. Truncated tau was being produced in neuron-glial cultures, while the production in neuron-enriched cultures did not occur, suggesting that glial cells are linked to it. Based on these evidences, the main aims of this project are to investigate the role neuron-glial interactions in the production of truncated tau and their relevance to AD. Two types of primary culture, neuron-enriched and neuron-glial cultures, were prepared from rat cortical neuron cells and treated with different compounds. Proteins were collected and an analysis of tau and other neuron-glial proteins was done by western blotting. Complementary, immunocytochemistry experiments and metabolic flux analysis were carried out to study other possible factors relevant for the production of truncated tau. Results revealed that an optimal production of 36 kDa was achieved when cultures were treated with full media change including zinc or glutamate. Glutamate stimulation of cultures induced the production of small fragments of truncated tau, possibly due to an excessive neuronal excitation which caused glutamate excitotoxicity. Microglial activation and metabolic changes did not seem to be relevant for the production of truncated tau. In any case, more replicates are needed to confirm results obtained and further experiments are needed to determine the specific mechanism by which truncated tau is being generated

More information

Item ID: 57007
DC Identifier: http://oa.upm.es/57007/
OAI Identifier: oai:oa.upm.es:57007
Deposited by: Biblioteca ETSI Agrónomos
Deposited on: 22 Oct 2019 08:42
Last Modified: 22 Oct 2019 08:42
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