Patients with motor neurone disease produce toxic proteins which kill off vital nerve cells, researchers found.
Cells are lost in the brain
The proteins, immunoglobulins (IgG), cause calcium levels in cells that control movement to rise too high, leading to degeneration and death.
It is hoped the discovery could lead to new ways to treat the condition.
The study, by the Institute of Neurology at University College London, is published in journal Acta Neuropathologica.
The researchers, who were funded by the charity Action Medical Research, found that IgG taken from health individuals did not produce the same effect.
MND is caused by the death of cells - called motor neurones - that control movement in the brain and spinal cord.
It affects around 5,000 people in the UK at any one time and there are 1,000 new cases of disease each year.
Symptoms of MND are muscle weakness in one or more limbs and also the muscles that supply the face and throat, causing problems with speech and difficulty chewing and swallowing.
But by the time the patient first notices any muscle weakness or swallowing difficulty, it is estimated up to 50% of their neurones have already died.
In the majority of cases the intellect is not affected.
Death usually occurs in around three to ten years due to paralysis of the respiratory muscles.
About 10% of MND is genetic but the cause of 90% cases are unknown, although several factors are probably important.
There is no cure for the condition, only treatments to relieve symptoms such as excessive pain from muscle cramps, salivation, difficulties with swallowing and speech, and respiratory and psychological distress.
Lead researcher Dr Anthony Pullen said: "Our work has allowed us to see both the initial and end stages of how motor neurones die in the laboratory.
"We are just beginning to understand how immunoglobulins and calcium react in nerve cells, but we need to do a lot more work to understand the mechanism and the real significance for MND.
"There is a lot of exciting work going on in MND research which will hopefully lead to the development of drugs that will really help people with Motor Neurone Disease."
Simon Moore, chief executive of Action Medical Research said: "This work could potentially lead to the development of some treatments which will help these people.
"Early intervention is always desirable in most diseases and it would help enormously if progress could be made in this area."