アルツハイマー病の基礎知識
Hello everyone, welcome to SCIEN-SPOT. This podcast shines a spotlight on the latest scientific
technology from Japan. Your host is REN from SCIEN-TALK. Today's topic is the Alzheimer's
disease and most people likely associate with the condition where brain functions such as memory
gradually deteriorate. One of the major causes of this disease is believed to be a protein called
amyloid beta. When this amyloid beta abnormally accumulates in the brain and self-assembles into
fibers, a process called fibrillation is thought to be the key to the onset of the disease. You
can imagine it like tiny pieces of garbage accumulating in the brain, tangling up and
forming large clumps that hinder brain function. However, there are various types of amyloid beta
and particularly for familial Alzheimer's disease which is a radical form and the detailed
structures of many mutant amyloid beta types remained unsolved. So I'm highlighting a particularly
鳥取型変異アミロイドベータの研究
fascinating study on the familial mutant amyloid beta called Tottori type. This Tottori type
Tottori型アミロイドβの挑戦
amyloid beta is characterized by a D7N mutation where the aspartic acid D at the seventh position
in amyloid beta's amino acid sequence is replaced by the asparagin N. It was known that this mutant
amyloid beta exhibits unusual aggregation behavior. So why has the structural analysis of this Tottori
type beta been so challenging until now? The problem is that when experiments are conducted
on earth, this Tottori type beta tends not to form ordered amyloid fibrils
and instead it forms chaotic irregular masses known as amorphous aggregates.
Imagine trying to build a specific shape with building blocks but instead they always just
pile up into a messy heap making it impossible to discern any clear shape. This makes it incredibly
difficult to study its structure in detail. This is where the research team turned their attention
to an unexpected place, space. A research group centered at the Exploratory Research Center on
Life and Living Systems used the Kibo, Japanese experiment module on the International Space
微小重力とフィブリルの形成
Station. In space, under microgravity conditions, gravity-induced convection and
sedimentation which occur in earth are suppressed. This allowed them to limit the formation of
amorphous aggregates and efficiently promote the formation of high-quality targeted fibrils.
To give you an analogy, if you put sugar in water on earth, gravity causes a denser sugar to sink
and the convection can make it difficult to dissolve uniformly. But in the microgravity
environment of space, these forces are largely absent, allowing for more precise control over
materials. Thanks to this unique microgravity environment, TOTRI type A beta, which was
previously impossible to analyze, was able to fabricate like a perfectly ordered crystal,
making detailed structural investigations possible. For the structural analysis,
they used a highly advanced microscope called cryo-electron microscope. This technique allows
researchers to observe frozen samples using an electron beam, revealing incredibly tiny
structures as nanometers to atomic levels. It's like taking ultra-high-resolution photographs
微小重力環境の影響
of molecular blueprints. The results of this analysis revealed a surprising fact.
In the fibril structure of TOTRI type A beta, the N-terminal region of the protein was found
to be flexible and lack the order structure. This suggests that the N-terminal core structure
stabilization mechanism seen in wild type or normal A beta is lost in the TOTRI type.
The D7N mutation is believed to cause changes in charge balance and an increase
in hydrophobicity, which in turn promotes amorphous aggregation and hinders proper
fibrillation formation. In essence, this mutation was the reason why A beta couldn't
form proper fibers and instead created disordered clumps. This study is the first to structurally
demonstrate how a microgravity environment affects protein aggregation processes.
It holds significant potential for advancing our understanding of Alzheimer's diseases,
pathology, and for developing new structure-based therapeutic drugs.
It's truly like something out of science fiction, isn't it? That experiments in space are helping us
宇宙でのアルツハイマー研究
find keys to protect our health. So that's all for today's science put. This podcast is
broadcast daily on weekday morning in both Japanese and English. Next week,
I'll be temporarily returning to Japan from London, so I might only be able to broadcast on Monday.
I'll share more in Monday's episode, but I recently appeared on a show for Nippon Broadcasting.
This is a Japanese radio station. Look out for that, as both Japanese and English versions will
be available. I'd love for you to listen to the podcast and parse your notes and thoughts
with the hashtag science put. See you next time.
