The latest research on neurodegenerative disease shows that not only can you prevent neurodegenerative diseases such as Alzheimer's and. A neurodegenerative disease is a disorder caused by the deterioration of neurons. . activate alpha-secretase, which can prevent AD amyloid neuropathology. J UOEH. Jun 1;38(2) doi: /juoeh Natural Compounds Preventing Neurodegenerative Diseases Through Autophagic Activation.
Disorders Prevents Neurodegenerative
However, with age, these defence systems become gradually less efficient, leading to accumulation of misfolded proteins and this is devastating for cells and organisms where accumulation of misfolded proteins is central to the development of neurodegenerative diseases.
This research could be the first step towards developing drugs to prevent neurodegenerative diseases. When given to mice, the small molecule prevents the motor, histological and molecular defects of two otherwise unrelated protein-misfolding diseases in mice, Charcot-Marie-Tooth 1B and amyotrophic lateral sclerosis.
This was achieved without any side effects. With age, the cellular defence systems against misfolded proteins seem to gradually fail, leading to the accumulation of misfolded proteins, with devastating consequences for cells and organisms. The small-molecule was named Sephin1 because it is a specific inhibitor of a holophosphatase. Before this study, phosphatases were thought to be undruggable, in contrast to kinases, which are popular drug targets.
The discovery of Sephin1, that safely prevents two diseases in mice represents a novel therapeutic modality. Neuroscience News would like to thank Anne Bertolotti for submitting this article to us. Published online April 10 doi: Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit.
Protein phosphorylation regulates virtually all biological processes. Although protein kinases are popular drug targets, targeting protein phosphatases remains a challenge.
Here, we describe Sephin1 selective inhibitor of a holophosphatase , a small molecule that safely and selectively inhibited a regulatory subunit of protein phosphatase 1 in vivo.
Sephin1 selectively bound and inhibited the stress-induced PPP1R15A, but not the related and constitutive PPP1R15B, to prolong the benefit of an adaptive phospho-signaling pathway, protecting cells from otherwise lethal protein misfolding stress. In vivo, Sephin1 safely prevented the motor, morphological, and molecular defects of two otherwise unrelated protein-misfolding diseases in mice, Charcot-Marie-Tooth 1B, and amyotrophic lateral sclerosis.
Indeed, the researchers concluded that the evidence suggests that one stage of the pathophysiology leading to AD is characterized by an inflammatory process. Additional research is necessary before recommendations can be made for people to take NSAIDs to keep neurodegenerative disease at bay. Scientists have noticed that patients with AD tend to have lower antioxidant status. Recent autopsy findings on study patients with amnestic mild cognitive impairment demonstrate that oxidative damage may be an early event in the pathogenesis of AD.
The researchers suggest that better antioxidants and agents used in combination to upregulate defense mechanisms against oxidation will be required to neutralize the oxidative component of the pathogenesis of AD. Perlmutter sums it up: Neurodegenerative diseases represent the downstream effects of excessive free radical activity, supporting antioxidant approaches to brain protection and functional enhancement.
Protecting the Brain Through Diet How can people practice smart eating to protect the brain from neurodegenerative disease?
Perlmutter suggests several nutritional approaches that show particular promise. A growing body of research links DHA with brain health. Epidemiological data indicate that DHA may be associated with a reduced risk of AD, while observational studies have found that lower DHA status is associated with an increased risk of AD. Data from several animal models support the hypothesis that DHA may be an effective treatment for AD because of antiamyloid, antioxidant, and neuroprotectant mechanisms.
A National Institutes of Health-funded, randomized, double-blind, placebo-controlled trial on the effects of DHA in slowing the progression of AD is currently underway. Calorie Restriction Long linked with longevity in mammals, calorie restriction may protect against neurodegenerative pathology, according to Perlmutter.
Calorie restriction induces sirtuins, silent information regulator proteins that regulate life span, enable DNA repair, protect DNA, and improve the survival of neurons.
Researchers from the Mount Sinai School of Medicine used an experimental mouse model to demonstrate that beta-amyloid peptides in the brain can be reduced by subjecting the mice to dietary caloric restriction, primarily based on low-carbohydrate food. Conversely, a high caloric intake based on saturated fat was shown to increase levels of beta-amyloid peptides.
The study, which was published in a issue of The Journal of Biological Chemistry , suggested that caloric restriction through the promotion of the sirtuin SIRT1 may activate alpha-secretase, which can prevent AD amyloid neuropathology.
Additional research needs to further clarify the role of calorie restriction in neurodegenerative disease. Polyphenols The most abundant antioxidants found in the diet, polyphenols have shown neuroprotective effects in studies over the past decade. Researchers have found that these plant compounds are able to protect neuronal cells in various in vivo and in vitro models through different intracellular targets.
It appears that the mechanisms of action for dietary polyphenols extend beyond their antioxidant activity. For example, researchers from the USA National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research and Department of Pharmacology and the Rappaport Family Research Institute in Israel report that green tea catechin polyphenols, thought to be simple radical scavengers, are now considered to promote a spectrum of cellular mechanisms of action related to neuroprotective activity.
These include activities such as iron chelation, scavenging radicals, activating survival genes and cell signaling pathways, and regulating mitochondrial function and possibly of the ubiquitin-proteasome system. Curcumin The compound that lends the popular Indian spice curry its bright-yellow color may have the power to protect against AD, according to UCLA researchers. India, where curcumin is consumed regularly, boasts one of the lowest rates of AD in the world.
Curcumin appears to slow the formation of—and possibly even destroy—accumulated plaque deposits at the root of AD. Curcumin significantly lowered oxidized proteins and interleukin-1beta, a proinflammatory cytokine, in Alzheimer transgenic mice brains, according to a study in The Journal of Neuroscience.
Greg Cole, PhD, a professor of medicine and neurology at UCLA, who has studied the effects of curcumin on AD, reports that curcumin is a potent antiamyloid drug with an established safety profile that has reversed cognitive defects in animal models. Antioxidant Vitamins With the power to squelch oxidative damage associated with neurodegeneration, antioxidant vitamins may become an important strategy for neurodegenerative disease prevention.
A study in the Archives of Neurology found a reduced risk of AD in users of antioxidant vitamin supplements. Coenzyme Q10 Researchers believe that coenzyme Q10, a fat-soluble compound primarily synthesized in the body and also consumed in the diet, may have the potential to affect the course of neurological disease in which mitochondrial function is impaired and oxidative stress and damage are present, according to a article in Neurology.
Coenzyme Q10 is required for mitochondrial ATP synthesis and functions as an antioxidant in cell membranes and lipoproteins. A month, randomized, placebo-controlled trial published in the Archives of Neurology in investigated the effects of coenzyme Q10 on early PD. Coenzyme Q10 supplementation was well tolerated at all doses and associated with slower deterioration of function in patients with PD compared with placebo. Additional research is needed to confirm these results.
Mediterranean Diet Along with a host of disease-prevention benefits, the Mediterranean diet has also been linked with a lower risk of AD. In a case-control study in a New York community-based cohort, researchers discovered that higher adherence to the Mediterranean diet was associated with a lower risk of AD, possibly due to the reduction in inflammation and an antioxidant effect. Obesity seems to be on the top of the list of concerns.
Studies have shown that people with higher levels of adiposity are at higher risk for both future PD and AD and that central adiposity is related to cognitive decline and dementia.
Body fat may store toxins. Diabetes is linked with a higher risk of dementia and AD as well. Brain inflammation may also be bolstered by advanced glycosylation end products AGEs , molecules formed during a nonenzymatic reaction between proteins and sugar residues called the Maillard reaction.
First Step in Preventing Neurodegenerative Diseases
Worried about Alzheimer's disease and neurodegeneration? Most of us believe, to some degree, we can take steps to prevent heart disease, diabetes and. Neurodegeneration is the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases – including amyotrophic lateral sclerosis, .. Protein degradation offers therapeutic options both in preventing the synthesis and degradation of irregular proteins. There is also interest. Preventing Neurodegenerative Diseases By Studying Proteins In The Brain. Date : October 10, ; Source: American Society for Biochemistry and Molecular.