Dr. Nicolas G. Bazan. Credit: LSU Health New Orleans Neuroscience Center of Excellence
Understanding
how dietary essential fatty acids work may lead to effective treatments for
diseases and conditions such as stroke, Alzheimer's disease, age-related
macular degeneration, Parkinson's disease and other retinal and
neurodegenerative diseases. The key is to be able to intervene during the early
stages of the disease. That is the conclusion of a Minireview by Nicolas Bazan,
MD, PhD, Boyd Professor and Director, and Aram Asatryan, PhD, postdoctoral
researcher, at the Neuroscience Center of Excellence at LSU Health New Orleans
School of Medicine published in the Journal of Biological Chemistry's
Thematic Minireview Series: Inflammatory transcription confronts homeostatic
disruptions.
Docosahexaenoic
acid (DHA), a key essential Omega-3 fatty acid, produces signaling molecules
called docosanoids in response to disruptions in the state of equilibrium
within cells caused by injury or disease. Neuroprotectin D1 (NDP1) is a
docosanoid that the Bazan lab discovered and found protects neurons by
controlling which and how certain genes in the retina and brain respond.
Research
shows that the preclinical events in Alzheimer's disease including
neuroinflammation, damage to dendritic spines - small doorknob-shaped
protrusions that help transmit electrical signals to the cell - and problems
with cell-to-cell communication coincide with decreased DHA content in the
brain. The neuroprotective bioactivity of NPD1 includes inflammatory modulating
properties as well as features that promote cell survival, both of which
contribute to restoring a stable state of equilibrium, or homeostasis, within
the cell.
In
experimental models of stroke, researchers at LSU Health New Orleans
Neuroscience Center led by Bazan have shown that the administration of NPD1
reduces the size of stroke damage and also saves tissue in the rim surrounding
the stroke core, which remains viable for a short time.
Research
has demonstrated that DHA from the liver is also retained and concentrated in photoreceptor
cells and that retinal
degeneration occurs when photoreceptor cells fail to capture DHA. When a gene
that regulates the uptake of DHA is turned off, photoreceptor cells die and a
single amino acid mutation in this receptor can cause retinitis pigmentosa.
Cells
die through a variety of mechanisms. Contributors include a family of reactive
oxygen species - compounds formed continuously as by-products of aerobic metabolism
such as from reactions to drugs and environmental toxins, or when the levels of
antioxidants are diminished creating oxidative stress, as well as inflammation
and the disease process. Cell death is considered to
be reversible until a first "point of no return" checkpoint is
passed. The authors describe how NPD1 acts to stop cells from passing that checkpoint in cell
death activation pathways including apoptosis, necrosis, necroptosis,
pyroptosis, and pyronecrosis, among others.
The
Minireview summarizes the effects of the essential fatty acid family member DHA
and its bioactive derivative NPD1 in the context of a specific target of gene
regulation. The authors also describe the mechanism of a pathway of regulation
by a bioactive lipid that has a significant impact on cellular homeostasis -
how NPD1 activates pro-survival genes and suppresses pro-death genes.
"The
organizational and functional complexity of the brain raises new questions
regarding how the cellular events described here operate in response to
disrupted homeostasis to attain neuroprotection in pathological
conditions," notes Bazan. "It is our hope that this knowledge will
contribute to managing early stages of such devastating diseases as
Alzheimer's, stroke, traumatic brain injury, age-related macular degeneration, Parkinson's
and others."
More information: Aram
Asatryan et al, Molecular mechanisms of signaling via the docosanoid
neuroprotectin D1 for cellular homeostasis and neuroprotection, Journal of Biological
Chemistry (2017). DOI:
10.1074/jbc.R117.783076
Journal reference: Journal of Biological Chemistry
Provided by: Louisiana State University
https://medicalxpress.com/news/2017-07-omega-fatty-acids-alzheimer-diseases.html
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