3. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characteri

Question

3. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the deterioration of motor neurons. While the pathogenesis of ALS is still poorly understood, one hypothesis of the mechanism of ALS is glutamate receptor-mediated excitotoxicity. One subunit of this glutamate receptor has an amino acid residue that could be a Gln or Arg. A. What is the protein that causes the change of the Gln to an Arg? B. Does this change occur on a DNA, mRNA, or protein level? What is the molecular change that occurs (specifically which nucleotide or amino acid)? How does this Gln to Arg change affect the function of the glutamate receptor?. C. D. How does a deleterious mutation in ADAR cause the excitotoxicity observed in ALS?

Explanation / Answer

Ans 1) The change of the Gln to Arg in Amyotrophic lateral sclerosis is aided with help of the FET protein. The protein is derived from three types of mutated genes which are –FUS, TAF15 and EWSR1. The protein is related to regulating the lifespan and neuronal integrity.

Ans 2) The change occurs in the genetic level and the change specifically takes place in the nucleotides. The mutations lead to formation of change in the genetic sequence and hence it is at the genetic level.

Ans 3) The Gln to Arg change affect the function of glutamate receptor as it inhibits the glutamate receptors from mediating fast excitatory synaptic transmission in the central nervous system. The change in the amino acid prevents the glutamate receptor from performing its neuronal function.

Ans 4) The excitotoxicity is caused by excessive and dysregulated activation of glutamate and something that is caused due to motor neuron death in ALS. ADAR is protein coding gene and it leads to conversion from A to I in the RNA that disrupts the normal A:U pairing that makes the RNA unstable. Inosine is structurally similar to guanine and leads to I to cytosine binding.

Related Questions

Navigate

• Browse (All)
• Browse 3
• Subjects

---

---

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.