Question

Select a human disease or disorder of a cellular organelle or the cytoskeleton. Provide 1 page review of the disorder, including a molecular and cellular characterization as well as essential clinical features. If an animal model (transgenic, knockout, or other) is available for this disorder, address it in your review.

Answer 1

Amyotrophic lateral sclerosis or ALS, is a progressive nervous system (neurological) disease that destroys nerve cells and causes disability.

Pathophysiology :

It is not fully understood why neurons die in ALS, but this neurodegeneration is thought to involve many different cellular and molecular processes.

The genes known to be involved in ALS can be classified into three general categories based on their normal function: protein degradation, the cytoskeleton, and RNA processing. Mutant SOD1 protein forms intracellular aggregations that inhibit protein degradation. Cytoplasmic aggregations of wild-type (normal) SOD1 protein are common in sporadic ALS. It is thought that misfolded mutant SOD1 can cause misfolding and aggregation of wild-type SOD1 in neighboring neurons in a prion-like manner. Other protein degradation genes that can cause ALS when mutated include VCP, OPTN, TBK1, and SQSTM1. Three genes implicated in ALS that are important for maintaining the cytoskeleton and for axonal transport[10] include DCTN1, PFN1, and TUBA4A.[

Symptoms

Early signs and symptoms of ALS include:

Difficulty walking or doing your normal daily activities

Tripping and falling

Weakness in your leg, feet or ankles

Hand weakness or clumsiness

Slurred speech or trouble swallowing

Muscle cramps and twitching in your arms, shoulders and tongue

Difficulty holding your head up or keeping good posture

ALS often starts in the hands, feet or limbs, and then spreads to other parts of your body. As the disease advances and nerve cells are destroyed, your muscles progressively weaken. This eventually affects chewing, swallowing, speaking and breathing.

ALS doesn't usually affect your bowel or bladder control, your senses or your thinking ability

Complications

As the disease progresses, people with ALS experience complications, which may include:

Breathing problems

Over time, ALS paralyzes the muscles you use to breathe. You may need a device to help you breathe at night, similar to what someone with sleep apnea might wear. For example, you may be given continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BiPAP) to assist with your breathing at night.

Some people with advanced ALS choose to have a tracheostomy — a surgically created hole at the front of the neck leading to the windpipe (trachea) — for full-time use of a respirator that inflates and deflates their lungs.

The most common cause of death for people with ALS is respiratory failure. On average, death occurs within three to five years after symptoms begin.

Speaking problems

Most people with ALS will develop trouble speaking over time. This usually starts as occasional, mild slurring of words, but progresses to become more severe. Speech eventually becomes more difficult for others to understand, and people with ALS often rely on other communication technologies to communicate.

Eating problems

People with ALS can develop malnutrition and dehydration from damage to the muscles that control swallowing. They are also at higher risk of getting food, liquids or saliva into the lungs, which can cause pneumonia. A feeding tube can reduce these risks and ensure proper hydration and nutrition.

Dementia

Some people with ALS experience problems with memory and making decisions, and some are eventually diagnosed with a form of dementia called frontotemporal dementia.