MIT researchers have made a significant advancement in the effort to combat Alzheimer’s disease by achieving substantial reductions in neurodegeneration, according to a study. The breakthrough occurred when the team successfully targeted an enzyme, CDK5 (cyclin-dependent kinase 5), which is typically overactive in the brains of Alzheimer’s sufferers.
Using an unidentified peptide, or a chain of amino acids, the scientists treated the hyperactive CDK5 enzyme. Preliminary experiments on mice showed promising and substantial results. Li-Huei Tsai, the study’s author and director of MIT’s Picower Institute for Learning and Memory, explained that the peptide could penetrate the brain, protect against neuron loss, and potentially reverse some behavioral deficits.
With additional research, it is hoped that this peptide could serve as a treatment for dementia, particularly dementia resulting from CDK5 overactivity. CDK5 is activated by a smaller protein called P35, which can become harmful in Alzheimer’s patients when it is cleaved into an even smaller protein called P25, also linked to Parkinson’s disease. P25, in turn, causes CDK5 to become hyperactive, as reported by MIT.
Attempts to target P25 with small-molecule drugs have been unsuccessful due to side effects caused by interference with other cyclin-dependent kinases. Therefore, none of these drugs have been tested on patients. Instead, Tsai and her team used the peptide to target P25, which led to numerous beneficial effects in a mouse model of Alzheimer’s with hyperactive CDK5, including reduced DNA damage, neural inflammation, and neuron loss.
The peptide has also shown promise in repairing altered tau proteins, a key feature of Alzheimer’s disease. Additionally, the study found that the peptide could cross the blood-brain barrier and reach neurons in the hippocampus and other brain regions, resulting in behavioral improvements. Future research will explore the peptide’s effects on diabetes-related cognitive impairments and other neurodegenerative diseases.
Scientists are hopeful about these new findings. Dr. Stuart Lipton, a neuroscience professor at Scripps Research, noted that further development of such peptide inhibitors could lead to novel treatments for neurodegenerative disorders ranging from Alzheimer’s to frontotemporal dementia to Parkinson’s disease, provided they are selective for the target and relatively free of clinical side effects.
Comments: CDK5 plays a crucial role in various cellular processes, including neuronal development, cell migration, and synaptic plasticity. Aberrant CDK5 activity has been implicated in several neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. As a result, CDK5 has emerged as a potential therapeutic target, and researchers have been investigating natural compounds that can inhibit CDK5 activity. Some of these compounds include:
- Flavonoids: A group of naturally occurring compounds found in various fruits, vegetables, and plant-derived beverages. Some flavonoids, such as apigenin, luteolin, and quercetin, have been reported to inhibit CDK5 activity in vitro.
- Curcumin: A polyphenolic compound derived from the rhizome of Curcuma longa (turmeric) that has been shown to exhibit anti-inflammatory, antioxidant, and anticancer properties. Curcumin has also been reported to inhibit CDK5 activity in preclinical studies.
- Resveratrol: A polyphenolic compound found in grapes, red wine, and some berries. Resveratrol has been shown to possess various health-promoting effects, including antioxidant, anti-inflammatory, and neuroprotective properties. Some studies suggest that resveratrol can inhibit CDK5 activity.
- Epigallocatechin gallate (EGCG): A catechin found in green tea that possesses antioxidant, anti-inflammatory, and neuroprotective effects. EGCG has been reported to inhibit CDK5 activity in vitro.
In addition to CDK5, recent studies have shown that targeting SIRT1 (silent information regulator 1) may also have a significant neuroprotective effect. Natural compounds that can upregulate SIRT1 include:
- Resveratrol
- Pterostilbene
- Quercetin
- Curcumin
- L-theanine
- Extra virgin olive oil
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