Cell Penetrating Peptides in Neuroscience

 

Cell penetrating peptides (CPPs) are a class of small peptides that can cross the cell membrane. CPPs have the ability to transport molecules such as nucleic acids, proteins, drugs, and imaging agents into cells, making them an important focus in disease and diagnostic research. Of particular interest is their potential impact on conditions of the central nervous system, as CPPs have the ability to cross the blood brain barrier with their attached molecules.

The blood brain barrier is a protective mechanism of the central nervous system (CNS) that is designed to maintain homeostasis and protect the system from toxins. The blood brain barrier is made up of 4 parts: a capillary basement membrane, endothelial cells, pericytes, and astrocytes. These parts work together through the creation of tight junctions and enzyme barriers to help keep the CNS healthy.

The blood brain barrier serves as a strong protectant for the CNS. However, when diseases and conditions affect the CNS, the blood brain barrier poses a challenge in delivering drugs and therapeutics for treatment. More than 90% of small-molecule and almost 100% of large molecule therapeutics cannot pass through the blood brain barrier. Research is exploring cell penetrating peptides in the treatment of CNS conditions, as they are one of the select molecules that can pass through this barrier.

Brain Cancer

Gliomas are the most common type of cancer affecting the central nervous system. There are multiple types of gliomas, with glioblastoma being the most aggressive and lethal. Current treatment of glioblastoma involves surgical resection, followed with chemotherapy and radiation therapy. Complete surgical resection is difficult due to the invasive nature of glioblastoma and lack of clean margins, which often results in the growth of secondary tumors. Thus, researchers are looking for alternative, more effective, and less invasive treatment options.

Multiple studies have evaluated the possibility of using cell penetrating peptides to deliver genetic material, anticancer drugs, and nanoparticles to treat glioblastoma. Studies involve pairings such as siRNA with TAT and doxorubicin with penetratin. The peptide p28, having anticancer properties itself, has been paired with diagnostic labels to determine tumor margins as well as paired with TMZ treatment to increase effectiveness. In general, studies have yielded promising results, with conjugations leading to the reduction in growth and development of gliomas, killing of cancerous cells, and improved distribution of therapeutic agents in the brain.

See the range of bioreagents we carry for glioma research 

Ischemic Stroke

Ischemic stroke is a condition in which the blood vessels in the brain become blocked by a blood clot or plaque. This blocking prevents oxygen and nutrients from reaching the brain, causing cell death within minutes. Stroke is a large health concern, with a high disability and mortality rate and few effective treatments, driving researchers to look for new treatment options.

Researchers have explored the use of cell penetrating peptides with ischemic stroke. Different methods of treatment have been studied, including reducing neuroinflammation, addressing cell excitotoxicity, and exploring neuroprotection. Studies have yielded promising results for the development of new therapeutic treatments in these areas.

See the range of bioreagents we carry for research in strokes 

Neurodegenerative Diseases

Due to their ability to cross the blood brain barrier, CPPs are being studied as a possible therapeutic mechanism for neurodegenerative diseases, such as Alzheimer’s Disease, Huntington’s Disease, and Parkinson’s Disease. While there are treatments that target symptom presentation, there aren’t any current effective treatments for addressing the causative disease.

Pituitary adenylate cyclase-activating polypeptide (PACAP), a cell penetrating peptide, is of particular interest to scientists. Not only can this peptide cross the blood brain barrier, but the peptide itself possesses neuroprotective properties. Researchers are studying the effects of this peptide as a therapeutic agent. For example, low levels of this peptide are associated with cognitive decline in Alzheimer’s Disease. Treatment with this peptide has shown neuroprotective effects against Aβ-amyloid-42 oligomers and decreased progression of the disease. This peptide has also shown neuroprotective effects in Parkinson’s Disease, preventing the degradation of neurons and slowing cognitive decline.

Researchers are also studying the impact of pairing cell penetrating peptides with nanoparticles. Nanotechnology offers many advantages, including particle size, shape, and the ability to control the structure and design of particles. These traits allow for increased cellular uptake and decreased side effects due to particle specificity.

See our range of bioreagents for neurodegenerative disease research 

 

References

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• Kang, Y.C., Son, M., Kang, S. et al. Cell-penetrating artificial mitochondria-targeting peptide-conjugated metallothionein 1A alleviates mitochondrial damage in Parkinson’s disease models. Exp Mol Med 50, 1–13 (2018). https://doi.org/10.1038/s12276-018-0124-z
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