SOD1

By Yoskaly Lazo-Fernandez, PhD

Alzheimer’s Disease (AD) is a neurodegenerative disorder that is characterized by an abundance of the beta-amyloid peptide in the brain.  When AD was first discovered, it was determined that beta-amyloid was produced as a result of the proteolysis of the amyloid precursor protein (APP).  Aside from its role in AD, the single-pass transmembrane APP has a high expression level in the brain and tends to concentrate at the synapses of neurons.  Because of this localization, it has been suggested that APP plays a role in synapse formation and potentially plasticity.  However, the

During times of cellular stress overloading of the protein folding machinery leads to the accumulation of incorrectly folded proteins. This triggers the unfolded protein response (UPR) in order to try to reestablish homeostasis or, if this fails, to induce apoptosis. The UPR pathway is mediated by a group of ER-associated transmembrane receptors including activating transcription factor 6 (ATF6). The presence of misfolded proteins is monitored by BiP, an Hsp70 family member.

During autophagy ubiquitinated cargo or substrates are engulfed in a double-membrane autophagosome and transported to the lysosome for degradation. This process is important for maintaining cellular homeostasis and for degrading damaged organelles or misfolded protein aggregates. p62, also known as sequestosome 1 (SQSTM1), is an autophagy receptor that recognizes and recruits cargo to the autophagosome through its interaction with Atg8.

Amyotrophic lateral sclerosis is a neurological disease which impacts motor neurons that are involved in muscle movement throughout the body. The progressive degeneration of neurons causes weakened muscles and can lead to paralysis. There is no cure for ALS, but riluzole has been used to help with the damage to the motor neurons.

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NeuN is a RNA-binding protein that modulates alternative splicing and is localized both to the nucleus and cytoplasm. It is a member of the RNA-binding FOX (RBFOX) family of splicing regulators which includes RBFOX1 (Fox-1/A2BP1) and RBFOX2 (Fox-2/RBM9). Each FOX family member is differentially expressed – RBFOX1 in neurons, heart, and muscle while RBFOX3 is exclusively limited to neurons.