Cell's exciting neuroprotective mechanisms combat neuroaging/degeneration

Researchers at the University of Virginia Health Center have discovered a molecule in the brain that coordinates the immune system's response to Alzheimer's and multiple sclerosis (MS), which has the potential to give doctors a boost to the body's ability to
fight these and other devastating neurological diseases.

The molecule, called a kinase, the researchers found, is essential
for clearing plaque buildup associated with Alzheimer's and preventing the buildup of debris that causes MS.
The researchers say it does this by directing
the activity of brain cleansers known as microglia.
These immune cells were once overlooked by scientists, but in recent years they have played a vital role
in brain health.

The researchers report that this important new finding may one day allow doctors to boost the activity of microglia to treat or protect patients
with Alzheimer's, multiple sclerosis and other neurodegenerative diseases.

"Doctors currently have no effective treatment for the underlying cause of most neurodegenerative diseases, such as Alzheimer's, Parkinson's or amyotrophic lateral sclerosis
.
In our study, we discovered the master controller of cell types and processes needed to protect the brain from these diseases," said
John Lukens, Ph.
D.
, a senior researcher at the University of Virginia School of Medicine and its Center for Immune and Glial Cells (BIG), Carter Center for Immunology, and the University of Virginia Brain Institute.
"Our work further demonstrates that targeting this new pathway provides an effective strategy to eliminate the toxic culprits that cause impaired memory loss and motor control in neurodegenerative diseases
.
"

Toxic brain accumulation

Many neurodegenerative diseases, including Alzheimer's and multiple sclerosis, are thought to be caused by
the brain's inability to remove its own buildup of toxins.
Recent advances in neuroscience research have shed light on the importance of microglia in removing harmful debris from the brain, but UVA's new findings offer practical insight into how this clearance process happens — and the dire consequences
when it doesn't.

Using mouse models of Alzheimer's, the University of Virginia researchers found that a lack of the molecule they recognized, the spleen tyrosine kinase, triggered the buildup of plaque in the brain and caused mice to experience memory loss — just like
the symptoms of Alzheimer's in humans.
In addition, neuroscientists were able to reduce plaque buildup by activating this molecule and microglia in the brain, which offers a potential treatment for human patients, although this requires more research and testing
.

Researcher Hannah Ennerfelt said: "Our work describes a key factor
in microglial function in Alzheimer's disease and multiple sclerosis.
" She is the first author
of a new scientific paper outlining the findings.
"Understanding the underlying biology of these cells during neurodegeneration allows scientists and physicians to develop increasingly informed and effective therapeutic interventions
.
"

Meanwhile, in mouse models with multiple sclerosis, a lack of this molecule led to damage
to myelin, the protective layer on nerve cells.
When myelin is damaged, cells cannot transmit messages properly, leading to multiple sclerosis symptoms such as impaired mobility and muscle spasms
.
Researchers at the University of Virginia conclude in a new scientific paper that the molecule they found, simply SYK, is "critical"
in the critical process of removing myelin fragments.

"If increasing the activity of SYK in microglia can reduce the amount of myelin fragments in MS lesions, then developing new drugs that target SYK could stop the progression of MS and help reverse damage," said Elizabeth L.
Frost, Ph.
D.
, a
key investigator on the project.
"Given that most current drugs for multiple sclerosis suppress adaptive immunity, this is a particularly promising option
.
" These immunosuppressive drugs lead to susceptibility to infection and a high risk of potentially fatal side effects, such as progressive multifocal leukoencephalopathy
.
In addition, some forms of multiple sclerosis do not have a strong immune system involved, so treatment options for these patients are currently very limited
.
”

"Targeting SYK in microglia will bypass the multiple limitations
of current multiple sclerosis treatments.
"

Based on their promising results, the researchers report that targeting this molecule to stimulate the brain's immune activity could treat not only Alzheimer's disease and multiple sclerosis, but also a range of neurodegenerative diseases
.

"These findings are particularly exciting because they point to a therapeutic avenue where we can change the behavior of these native brain cells, microglia, in a more neuroprotective way," said researcher Coco Holliday, an undergraduate at
the University of Virginia.
"It could be applied to a variety of different neurological disorders that have problems
with the accumulation of toxic waste in the brain.
" It's a very exciting project
.
”

More information >> for Takara human iPS-derived microglia (Y50045) is welcome