Question

What is the effect of Hunington disease on the neurons in the central nervous system?

Answer 1

Huntington's disease results in the degeneration and death of specific neurons in the central nervous system due to a genetic mutation. Symptoms include movement disorders, cognitive impairment, and personality changes, occurring typically in midlife with a 50% chance of being passed to offspring.

Step-by-step explanation:

Huntington's disease is a genetic neurodegenerative disorder that leads to the death of neurons in the central nervous system, particularly affecting cortical and striatal neurons. It is characterized by a mutation in the gene that encodes for the huntingtin protein. This mutation gives rise to an abnormally elongated sequence of glutamine residues which seems to be linked to dysregulation in the expression of NMDA receptors. In Huntington's disease, the damage is primarily to GABAergic medium-sized spiny neurons, which ultimately results in a range of symptoms that include involuntary spastic movements, difficulty in initiating voluntary movements, cognitive decline, muscle spasms, and personality changes.

Neurons affected by Huntington's disease can show disruptions to mitochondrial membrane potential leading to cell death. This is exacerbated by increases in intracellular calcium concentrations due to extrasynaptic NMDA receptor activity. While synaptic NMDA receptor activity tends to be beneficial, the extrasynaptic receptor activity triggers harmful cellular pathways. Unfortunately, Huntington's disease is progressive and presently incurable, with symptoms not typically manifesting until middle age, which can complicate family planning due to a 50% chance of inheritance if one parent carries the mutated gene.

Answer 2

Huntington's Disease is a genetic neurodegenerative disorder leading to the progressive death of neurons in the CNS, particularly GABAergic neurons, due to an abnormal huntingtin protein affecting NMDA receptor activity. It presents with involuntary movements, cognitive decline, and has a 50% chance of inheritance if one parent carries the disease. Treatments aim to protect neurons from calcium-induced toxicity at extrasynaptic sites.

Step-by-step explanation:

Impact of Huntington's Disease on Central Nervous System Neurons

Huntington's Disease (HD) is a neurodegenerative disorder caused by a genetic mutation, where cortical and striatal neurons, particularly GABAergic medium-sized spiny neurons, undergo progressive degeneration. This results in the loss of neurons that disrupts normal brain function, leading to physical, psychological, and cognitive symptoms often characterized by involuntary movements, cognitive decline, and personality changes. The damaged neurons are specifically linked to motor control and cognitive processes, wherein the disease leads to the production of a huntingtin protein with an abnormal glutamine repeat expansion. This toxic protein variant disrupts cellular processes, including the regulation of NMDA receptors at synapses and extrasynaptic locations, which ultimately can cause disruptions in mitochondrial membrane potential and induce neuron death.

The inheritance pattern of HD is autosomal dominant, meaning that individuals with one affected allele have a 50% chance of passing the disorder to their offspring. Symptoms typically do not manifest until middle age, often after the individual has already reproduced. This delayed onset allows the disease to perpetuate through generations before the effects become apparent. While there is currently no cure for HD, research into treatments such as memantine and NR2B subunit specific antagonists focus on preserving neuron function by selectively blocking harmful extrasynaptic NMDA receptor activity without inhibiting their normal synaptic function.