17

March 2024 ESRFnews

NEURODEGENERATION

A

t the turn of the 20th Century, a 51 year-old

woman was admitted into the mental hospital

in Frankfurt, Germany. She could neither

recognize her own name, nor remember the names of

objects she had just been looking at; she kept claiming

she had “lost herself”. As her condition worsened, it was

studied obsessively by an anatomist who was interested

in neural pathology He made extensive notes and after

she died five years later conducted a biopsy of her brain

concluding that her symptoms originated in its outer

layer the cortex

That anatomists name was Alois Alzheimer

We are now well over a century into the study of

Alzheimers disease and we still do not know its cause

or how to cure it Researchers still believe as Alzheimer

did that it affects the cerebral cortex specifically in

the build up of proteins known as betaamyloids and

taus These seem to make it harder for neurons to

communicate as they should leading to memory loss

reasoning difficulties impaired language and mood

swings. But what prompts the build up of these proteins

is unknown, and even their roles are in question. Are

they actually the cause of the neurodegeneration, or are

they in fact just a symptom themselves – a scapegoat for

an entirely different pathological mechanism?

Many scientists believe we need to pursue different

hypotheses. One such scientist is Montserrat Soler-

López the leader of the ESRFs structural biology group

For about a decade she has been pursuing an unusual

idea that the root cause of Alzheimers actually lies in

the breathing apparatus of individual brain cells Now

armed with the ESRFs worldleading crystallography

spectroscopy and imaging capabilities she is getting some

surprising results

In many respects the neuron is similar to other types

of animal cell Within its body lies a nucleus where

the genetic information is kept and various other

specialised components or organelles including

mitochondria which produce energy for the cell to feed

on The mitochondria do this via a form of respiration

T he key to Alzheimer’s could lie in mitochondria,

the centres of cellular respiration.

Mind breathing

Above: Cryo-EM

image of the

structure of the

ACAD9–ECSIT

complex, which

assists in the

assembly of the

first protein mega-

complex involved

in mitochondrial

respiration ECSIT

shown in red