Scientists unravel molecular mechanisms of Parkinson's disease
Detailed brain cell analysis has helped researchers uncover new mechanisms thought to underlie Parkinson's disease.
The study, published in Nature Communications, adds to our growing understanding of the causes of Parkinson's and other neurodegenerative diseases, and could influence drug design in the future.
For years, scientists have known that Parkinson's disease is associated with a build-up of alpha-synuclein protein inside brain cells. But how these protein clumps cause neurons to die was a mystery.
Using a combination of detailed cellular and molecular approaches to compare healthy and clumped forms of alpha-synuclein, a team of scientists at the Francis Crick Institute, UCL, UK Dementia Research Institute at the universities of Cambridge and Edinburgh, New York University and other collaborators have discovered how the protein clumps are toxic to neurons.
They found that clumps of alpha-synuclein moved to and damaged key proteins on the surface of mitochondria – the energy powerhouses of cells – making them less efficient at producing energy. It also triggered a channel on the surface of mitochondria to open, causing them to swell and burst, leaking out chemicals that tell the cell to die.
These findings were replicated in human brain cells, generated from skin cells of patients with a mutation in the alpha-synuclein gene, which causes early-onset Parkinson's disease. By turning patient skin cells into stem cells, they could chemically guide them into become brain cells that could be studied in the lab. This cutting-edge technique provides a valuable insight into the earliest stages of neurodegeneration – something that brain scans and post-mortem analysis cannot capture.
Sonia Gandhi, Group Leader at the Crick and UCL, and joint senior author of the study said: “Our findings give us huge insight into why protein clumping is so damaging in Parkinson's, and highlight the need to develop therapies against the toxic form of alpha-synuclein, not the healthy non-clumped form.”
Andrey Abramov, joint senior author of the paper said: “This study was a complex collaboration at the interface of chemistry, biophysics and biology, bringing scientists from different disciplines together to investigate a longstanding problem in Parkinson's research.”
Alle Nachrichten aus der Kategorie: Health and Medicine
This subject area encompasses research and studies in the field of human medicine.
Among the wide-ranging list of topics covered here are anesthesiology, anatomy, surgery, human genetics, hygiene and environmental medicine, internal medicine, neurology, pharmacology, physiology, urology and dental medicine.
Determination of glycine transporter opens new avenues …
… in development of psychiatric drugs Glycine can stimulate or inhibit neurons in the brain, thereby controlling complex functions. Unraveling the three-dimensional structure of the glycine transporter, researchers have now…
Metallic state of Ag nanoclusters in oxidative dispersion identified in situ
Oxidative dispersion has been widely used in the regeneration of sintered metal catalysts as well as the fabrication of single-atom catalysts. The consensus on the oxidative dispersion process includes the…
A COSMIC approach to nanoscale science
Instrument at Berkeley Lab’s Advanced Light Source achieves world-leading resolution of nanomaterials. COSMIC, a multipurpose X-ray instrument at Lawrence Berkeley National Laboratory’s (Berkeley Lab’s) Advanced Light Source (ALS), has made…