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The Remarkable Neuroprotective Benefits of Larazotide, Semaglutide (GLP-1) and Tirzepetide (GLP-1/GIP).
GLP-1 is an incretin hormone produced by intestinal L cells that have growth- factor-like and neuroprotective effects.[1,2,5] These 36 amino acid gut peptides, also known as Larazotide and Semaglutide operate through neural and hormonal pathways to regulate satiety, gut motility, and pancreatic islet function.[1,2,4,5] The pancreatic islet controls blood glucose levels that the Central Nervous System (CNS) relies on as its primary metabolic fuel.[3] Dysfunction in the pancreatic islet function causes Type 2 diabetes (T2DM) which is well known to be a factor for progressive neurodegenerative conditions such as Alzheimer's disease (AD), Parkinson's disease (PD), and others.[1] Current clinical trials testing GLP-1 receptor (GLP-1R) agonists demonstrate improvement in PD, AD, and diabetic patients.[1,2,3,7] The glucose-dependent insulinotropic polypeptide (GIP) is known as the GLP-1 "sister." GIP analogs, better known as Tirzepeptide, have recently demonstrated neuroprotective effects on illness, improving the GLP-1 efficacy.[1] According to recent research, overcoming insulin resistance in the brain decreases illness progress in AD, making these peptides reliable for analysis.[1,5] The GLP-1R is present in most brain regions like the hippocampus, neocortex, hypothalamus, and cerebellum, implying that GLP-1 plays a critical signaling role.[2] GLP-1 analogs also have anti-inflammatory properties essential for combating the neurodegenerative effects of chronic inflammation, which are well known to cause disease progression.[4]
GLP-1 Agonist Benefits and Neuroprotection:
One of the most remarkable GLP-1 functions lies in its role as a potent glucagon inhibitor in the periods following a meal, which is essential for maintaining the correct levels of glucose in the blood.[7] On the other hand, GIP enables glucagon release during fasting.[7] Since both have a crucial role in regulating glucose homeostasis, analogs have been well studied to develop treatments for T2DM and PD.[1,7] Furthermore, researchers have found that GLP-1 receptor agonists like the exendin-4 showed promising effects in their phase II clinical trial in PD patients.[2] Exendin-4 can decrease dopaminergic neurodegeneration and brain inflammation by inhibiting the recruitment and activation of glial cells in animal models.[2] Exendin-4 also has a beneficial impact on motor function and exhibited a shielding effect on CNS from illnesses.[3,4,7] These findings cause the development of GLP-1/GIP dual receptor agonists and PEGylated versions of exendin-4.[2] GLP-1/GIP dual receptor agonists have been demonstrated to cross the blood-brain barrier easily and significantly reduce the chronic inflammation response.[2,8]
GLP-1R key points.[1,2]
• The β-cell GLP-1R obtains signals from both GLP-1 and glucagon to control glucose-stimulated insulin secretion.
• Brain-derived GLP-1 is synthesized in the brainstem and generally distributed to numerous GLP-1Rs throughout the CNS.
GLP-1/GIP dual receptor agonists benefits.[1,2,4,5,6,8]
• Cross BBB easily
• Reduce chronic inflammation response
• Decrease dopaminergic neurodegeneration
• Present in most CNS regions
• Anti-inflammatory properties
• Improving motor behavior in animal models
• Decrease of alpha-synuclein (α-syn) levels
• Weight loss
• Lipid-lowering
