Accumulation of the protein aggregates is the leading cause of cellular dysfunction in neurodegenerative diseases. In physiological situation, the protein misfolding is sensed by the cellular control systems as a threat to the survival of neurons, which will be followed by an immediate neuronal response. Any delay to detect the misfolded proteins, may result in neuronal deterioration and progression of neurodegenerative disorders. Alzheimer’s disease (AD), the most common form of dementia among the elderly and the third leading cause of death in adults is associated with two main lesions, both as a consequence of protein aggregation: extracellular plaques made of beta-amyloid (Aβ) and intracellular neurofibrilary tangles (NFT) made of tau protein.
A large plaques of Beta amyloid (red) surrounds a neuron which is highly positive for phosphorylated m-TOR (green). Phosphorylated m-TOR reduces cell ability of autophagy, a critical process to clear beta-amyloid. Accumulation of tau protein in Neurofibrillary tangles (cyan) could be seen in another neuron above beta amyloid plaque. Image Credit: Neuronal Injury & Repair (NIR) Laboratory; Dr. Shohreh Majd)
Although the process of neuronal death is a common feature in Alzheimer’s disease, underlying mechanisms are still under investigation. In this scenario, Aβ and Neurofibrillary tangles are considered as the main neurotoxic proteins to initiate neurodegeneration.
(Video Credit: Nature Video)