ALS (amyotrophic lateral sclerosis) happens when the nerve cells that control muscles gradually die, but in most people we still don’t know exactly why this process starts.

Quick Scoop: The Core Idea

  • ALS is a disease where motor neurons (the nerves that control movement) in the brain and spinal cord degenerate and die.
  • When these neurons are lost, muscles no longer get signals, so they weaken, shrink, and eventually become paralyzed.
  • In about 90–95% of people, ALS appears “out of the blue” with no clear cause (this is called sporadic ALS).
  • Around 5–10% of cases are clearly inherited and run in families (this is familial ALS).

So, “why ALS happens” is usually a mix of genes, aging, and environmental/lifestyle factors that stress and damage motor neurons over time.

Two Big Categories: Sporadic vs Familial

1. Sporadic ALS (most cases)

Sporadic ALS means there is no obvious family history and no single trigger we can point to. Researchers think it develops when:

  • A person is born with certain subtle genetic risks (not always inherited in a clear way).
  • Over many years, they accumulate environmental “hits” (toxins, smoking, injuries, etc.).
  • After several “steps” of damage, the motor neurons can no longer cope and start to degenerate.

This is sometimes called a multi‑step model : several different molecular insults slowly add up until disease appears, often in mid–late adulthood.

2. Familial ALS (inherited cases)

Familial ALS happens because of a clear disease‑causing mutation that can be passed from parent to child, often in an autosomal dominant pattern (one copy of the mutated gene is enough).

Key points:

  • About 5–10% of all ALS cases are familial.
  • In these families, multiple relatives across generations may have ALS, sometimes alongside frontotemporal dementia (FTD).
  • The mutated genes disrupt crucial cellular processes—like how proteins fold, how RNA is processed, and how cells handle waste—and this eventually kills motor neurons.

What’s Going Wrong Inside the Cells?

Scientists have identified several cellular and molecular problems that seem to drive ALS, even when we don’t know the exact trigger.

Protein misfolding and clumps

  • In most sporadic ALS cases, a protein called TDP‑43 becomes misfolded and abnormally accumulates in neurons.
  • In some genetic forms, proteins made by mutated genes (like SOD1 or proteins from C9orf72 expansions) also misfold and form toxic aggregates.
  • These clumps disrupt normal cell functions and can be directly toxic to motor neurons.

Problems with RNA and gene regulation

  • TDP‑43 and several ALS‑related genes are involved in handling RNA, which is how cells read and use genetic instructions.
  • When these RNA‑processing systems break, many genes start being expressed incorrectly, and neurons gradually fail.

Oxidative stress and mitochondrial damage

  • Oxidative stress means an overproduction of reactive oxygen species that damage proteins, DNA, and cell membranes.
  • Mitochondrial dysfunction (mitochondria are the cell’s “power plants”) makes it harder for neurons to produce energy and survive long‑term stress.

Immune and inflammatory changes

  • Microglia (immune cells in the brain and spinal cord) can become overactive , releasing inflammatory molecules that worsen neuronal injury.
  • This doesn’t usually start ALS on its own, but it can accelerate damage once the process has begun.

Glutamate “excitotoxicity”

  • Glutamate is the main excitatory neurotransmitter in the brain.
  • In ALS, glutamate may build up and overstimulate neurons, letting too much calcium into cells and triggering cell death pathways.

Known Genetic Causes: Why Some Families Get ALS

A number of genes are now linked to ALS; some are especially important.

  • C9orf72
    • The most common known genetic cause of ALS worldwide.
* Involves a large expansion of a short DNA repeat sequence.

* Often associated with both ALS and frontotemporal dementia, suggesting shared mechanisms in nerve degeneration.
  • SOD1
    • One of the first genes discovered in ALS.
* Mutations lead to an abnormal form of the SOD1 protein that aggregates and becomes toxic.

* Accounts for a significant portion of familial ALS cases and has led directly to targeted therapies (e.g., SOD1‑silencing treatments).
  • Other ALS‑associated genes
    • Many others exist (such as FUS, TARDBP and more), each influencing protein handling, RNA processing, or cellular transport systems.
* Each gene may contribute a few “steps” in the multi‑step path toward motor neuron death.

Even with these discoveries, a large share of both familial and sporadic ALS still cannot be tied to a single known gene.

Environmental and Lifestyle Factors Under Study

No single exposure explains ALS, but several factors are linked with higher risk in population studies.

  • Smoking
    • Identified as a risk factor, with some evidence that women who smoke, especially after menopause, may have higher risk.
  • Environmental toxins and heavy metals
    • Possible links with exposure to lead, pesticides, solvents, and other industrial chemicals, though no single toxin has been confirmed as “the cause.”
  • Physical trauma and electric shock
    • Some studies suggest prior head injury, physical trauma, or electric shock may increase risk, but data are mixed.
  • Military service and certain geographic clusters
    • Elevated ALS rates have been reported in some military populations and in specific regions, raising questions about complex environmental exposures.

Importantly, most people with these exposures never develop ALS , and many people with ALS have none of them, which is why researchers believe it’s the combination with underlying genetic vulnerability that matters.

A Useful Way to Think About It

One modern view is:

ALS is not one disease with one cause, but a final common pathway where many different genetic and environmental insults converge to kill motor neurons.

In this “many roads to the same destination” model:

  1. Different people start with different genetic risks.
  1. Over decades, they experience different environmental exposures, injuries, infections, and life events.
  1. Multiple molecular problems accumulate (protein misfolding, oxidative stress, inflammation, glutamate toxicity, mitochondrial damage).
  1. Once enough steps have occurred, motor neurons become irreversibly damaged and symptoms of ALS appear.

This helps explain why ALS can start at different ages, progress at different speeds, and look slightly different from person to person.

Is There Anything “New” in the Latest News?

Research in the last decade and up to the mid‑2020s has been especially focused on:

  • Better understanding TDP‑43 and related protein pathology in sporadic ALS.
  • Gene‑targeted therapies for known mutations like SOD1 and C9orf72.
  • The role of the immune system and microglia, and whether calming inflammation can slow the disease.
  • How the “multi‑step” model works in real patients—how many steps, which ones, and how to interrupt them.

Even with these advances, we still cannot yet say exactly why ALS happens in a given individual , only describe risk patterns and what is going wrong biologically.

Mini FAQ

Is ALS contagious?
No. There is no evidence that ALS spreads from person to person like an infection.

Is it always inherited?
No. Most cases are not inherited in a clear way, although subtle genetic risks likely exist in many people with sporadic ALS.

Can lifestyle alone cause it?
Current evidence says lifestyle or environment alone is unlikely to cause ALS; they seem to act on top of genetic and age‑related vulnerability.

Information gathered from public forums or data available on the internet and portrayed here.