Amyotrophic lateral sclerosis

Definition

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons in the brain and spinal cord, leading to muscle weakness and atrophy. This condition is characterized by the misfolding of proteins, particularly superoxide dismutase 1 (SOD1), which can aggregate and disrupt cellular functions, contributing to the death of motor neurons.

5 Must Know Facts For Your Next Test

1. ALS was first described by French neurologist Jean-Martin Charcot in 1869 and is sometimes referred to as Charcot's disease.
2. Approximately 90-95% of ALS cases are sporadic, with no clear family history, while 5-10% are familial, linked to genetic mutations.
3. The hallmark symptoms of ALS include muscle weakness, difficulty speaking or swallowing, and eventually respiratory failure due to weakened muscles.
4. Current research into ALS focuses on understanding the mechanisms of protein misfolding and identifying potential therapeutic targets to slow disease progression.
5. Riluzole is currently the only FDA-approved drug for ALS that can modestly prolong survival and delay the progression of symptoms.

Review Questions

• How does protein misfolding contribute to the development of amyotrophic lateral sclerosis?
  • Protein misfolding plays a critical role in the development of amyotrophic lateral sclerosis by causing proteins like superoxide dismutase 1 (SOD1) to aggregate within motor neurons. These aggregates disrupt normal cellular functions and lead to neuronal death. Understanding this connection helps researchers develop strategies to target misfolded proteins in hopes of slowing the progression of ALS.
• Discuss the differences between sporadic and familial forms of amyotrophic lateral sclerosis, including their implications for research and treatment.
  • Sporadic ALS accounts for about 90-95% of cases and occurs without a clear genetic link, while familial ALS represents about 5-10% of cases that are inherited through genetic mutations. The familial form often provides insights into specific genetic mechanisms involved in the disease, allowing researchers to identify potential therapeutic targets. Understanding these differences helps tailor research approaches and treatment strategies for both forms of ALS.
• Evaluate the impact of oxidative stress on the pathophysiology of amyotrophic lateral sclerosis and its relevance for developing new treatments.
  • Oxidative stress significantly impacts the pathophysiology of amyotrophic lateral sclerosis by causing damage to motor neurons through increased free radicals that overwhelm cellular defenses. This stress contributes to protein misfolding and neurodegeneration seen in ALS. Research into antioxidants and therapies aimed at reducing oxidative stress holds promise for developing new treatments that may protect neurons from damage and improve patient outcomes.

Related terms

Protein misfolding: The process in which proteins fail to fold into their correct three-dimensional structures, leading to dysfunction and potential aggregation.

Neurodegeneration: The progressive loss of structure or function of neurons, often associated with diseases like ALS, Alzheimer's, and Parkinson's.

Oxidative stress: An imbalance between free radicals and antioxidants in the body, which can damage cells and is implicated in neurodegenerative diseases like ALS.