Role of Protein Misfolding in Neurodegeneration

Proper protein folding is crucial for cell development. It is more difficult for neurons than other cells to fight the effects of misfolded proteins. Specifically, in the endoplasmic reticulum, protein unfolding can occur due to a variety of internal and external stressors. 

Endoplasmic reticulum: Cell’s Highway System

The endoplasmic reticulum, a cell organelle, is significant to glucose metabolism. Glucose metabolism is central to energy consumption, and plays an important role in Alzheimer’s disease, as the brain needs a significant amount of energy to sustain activity. Alzheimer’s patients have demonstrated reduced transport of glucose to the brain, compared to patients without a neurodegenerative disorder. 

Protein folding is an important role of the ER. However, when cells are under stress, such as in neurodegenerative disease, proteins become misfolded. This accumulation of misfolded proteins can then lead to different pathways being affected. For example, neurotransmission can be altered, and the release of neurotransmitters. In Alzheimer’s disease, this would affect alpha-beta plaques. 

Neuroplasticity: The Effect of Unfolded Proteins

Neuroplasticity is an important concept in neuroscience, as it refers to the ability of the brain to adapt to changes and rewire itself to accommodate for cellular dysfunction. The plasticity of synapses is affected by unfolded proteins, as synapses are structures that allow for the neurons to send signals to other neurons and brain cells. With this plasticity impaired, signals will not fire at the same rate and it is more difficult for the cells to communicate with each other. When cellular communication is impaired, this leads to cognitive impairment, and eventually can cause a neurodegenerative disease such as Alzheimer’s or Parkinsons.