NL-GHK-Cu in the prevention of common diseases such as atherosclerosis, cataracts, diabetes, nephropathy, and Alzheimer's disease.

NL-GHK-Cu peptide therapy, owing to its antioxidant activity, may inhibit and help prevent numerous pathological processes associated with ocular tissues, neurodegenerative disorders, kidney disease, and conditions affecting the cardiovascular system.

Abstract: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are free radicals that play important roles in the human body, for example by participating in intracellular signaling cascades and in host defense against invading pathogens. An imbalance between free-radical production and endogenous antioxidant defenses may result in cellular oxidative stress, causing oxidative damage to key cellular components such as DNA, proteins, and membrane lipids. NL-GHK-Cu peptide therapy may help restore the balance between free-radical generation and endogenous antioxidant defenses, thereby suppressing pathological processes and, consequently, limiting the development of disease.

Keywords: NL-GHK-Cu; antioxidation; atherosclerosis; cataract; diabetes; nephropathy; Alzheimer’s disease

Introduction

The prophylactic use of NL-GHK-Cu peptide therapy in the pathological conditions referenced in the title—atherosclerosis, cataract, diabetes, nephropathy, and Alzheimer’s disease—relies primarily on the peptide’s capacity to support antioxidant defense. In some of these disease contexts, additional properties of NL-GHK-Cu further justify its consideration as an adjunctive element within preventive strategies aimed at inhibiting or reducing the risk of disorders of diverse etiologies.

Antioxidant Defense Mediated by NL-GHK-Cu

Free radicals and toxic end products of lipid peroxidation are implicated in atherosclerosis, cataract, diabetes, nephropathy, Alzheimer’s disease, and other serious pathological states primarily associated with aging. Reactive oxygen species (ROS) and reactive carbonyl species (RCS) are generated in cells in small amounts under physiological conditions and play important roles in cellular signaling and immune defense. A robust antioxidant network maintains equilibrium between free-radical production and removal, such that overall free-radical–mediated damage remains limited. However, during aging and in pathological states, this balance may shift toward the accumulation of free radicals, potentially leading to oxidative stress and, ultimately, cell death.

NL-GHK-Cu increases the expression of antioxidant genes and suppresses the expression of pro-oxidant genes. It increases expression of the oxidative/inflammatory transcription factor NF-κB as well as the expression of two NF-κB inhibitors, TLE and ILBP. In this way, it likely suppresses NF-κB protein activity.

Atherosclerosis

Atherosclerosis is a progressive arterial disease characterized by narrowing of the arterial lumen. Arteries supply tissues with essential oxygen and nutrients. Atherosclerosis may involve arteries supplying various organs, including the heart, brain, and kidneys; consequently, it may lead to hypoxia of these organs. The disease may begin developing in childhood and is initially asymptomatic. Symptoms typically appear once the artery is already narrowed by approximately 50%, most commonly after the age of 50. Clinical manifestations vary depending on which artery is affected. Common symptoms include shortness of breath, fatigue, and low back pain.

GHK-Cu in Atherosclerosis Prevention

NL-GHK-Cu influences mitochondrial processes, thereby reducing lipid peroxidation and, consequently, decreasing the risk of atherosclerotic disease; it may also mitigate existing symptoms as an adjunctive therapy.

Another aspect emerging from innovative studies on atherosclerosis is the influence of NL-GHK-Cu on activation of vascular endothelial growth factor (VEGF), whose activation in atherosclerotic disease has historically been regarded as pathological. At appropriate doses, however, NL-GHK-Cu therapy may exert the opposite effect—supporting prevention of the disease. Novel potential therapeutic methods are under intensive investigation. VEGF represents a principal angiogenic factor controlling vessel growth, vascular homeostasis, permeability, and vasodilation; thus, it is considered a potential therapeutic factor for ischemic heart disease and ischemic peripheral vascular disease.

NL-GHK-Cu may also suppress fibrinogen synthesis. NL-GHK-Cu was isolated as a plasma molecule that suppressed fibrinogen. Fibrinogen is best known for its role in blood clot formation, but it also affects microcirculatory flow, where blood behaves as a thixotropic fluid under pulsatile pressure changes. Elevated fibrinogen significantly increases blood viscosity in the microcirculation by promoting red blood cell “stacking” (rouleaux formation). These properties constitute further evidence supporting the capacity of NL-GHK-Cu to inhibit pathological processes associated with atherosclerosis.

Cataract

Cataract is an ocular disorder characterized by clouding of the crystalline lens. It may occur due to injury or the use of certain medications (e.g., corticosteroids). The most common form is age-related cataract, the precise causes of which are not fully understood. Cataract typically affects older adults, but it can also occur in younger individuals, for example those with myopia or diabetes. Cataract may be congenital or acquired.

GHK-Cu in Cataract Prevention

As noted above, cataract involves lens opacification caused by precipitation of water-insoluble protein compounds formed through free-radical–mediated oxidation. Free radicals are not sufficiently neutralized when antioxidant reserves become depleted with age; therefore, replenishing antioxidants through diet may be beneficial. As described earlier, NL-GHK-Cu increases the expression of antioxidant genes and suppresses pro-oxidant gene expression, which may help prevent or slow cataract development, both acquired and congenital forms.

Diabetes

Diabetes mellitus comprises a group of metabolic disorders characterized by chronic hyperglycemia resulting from impaired insulin secretion and/or insulin action. Insufficient insulin secretion and reduced tissue responsiveness to insulin compromise insulin’s complex actions in target tissues, leading to disturbances in carbohydrate, lipid, and protein metabolism. In affected individuals, defects in both insulin secretion and insulin function may be present.

GHK-Cu in Diabetes Prevention

Reactive oxygen species can induce cellular alterations and contribute to the development of diabetes as well as its subsequent complications. In diabetes, oxidative stress increases as the disease process persists and redox/antioxidant balance becomes disrupted. Protein and lipid peroxidation products are significantly elevated in patients with diabetes, while antioxidant concentrations are markedly reduced. Changes in antioxidant enzyme activity and glutathione levels suggest that these indicators may be useful in identifying and predicting disease progression. As noted, GHK-Cu may help maintain oxidative balance and thereby reduce the risk of diabetes and attenuate its manifestations.

Nephropathy

Nephropathy refers to kidney disease and may accompany various conditions. Most commonly, nephropathic changes occur in the context of diabetes. In healthy individuals, urine does not contain protein molecules. In individuals with diabetes, filtration disturbances and renal structural changes may develop over time, resulting in progressively increasing urinary protein excretion—an indicator of nephropathy.

GHK-Cu in Nephropathy Prevention

Free radicals attack not only the pancreas, stomach, and intestines, but also the kidneys, thereby contributing to nephropathy. NL-GHK-Cu increases expression of antioxidant genes and suppresses pro-oxidant gene expression. It increases expression of oxidative/inflammatory genes, which in this context is associated with inhibition of nephropathy progression as well as other renal disorders.

Alzheimer’s Disease

Alzheimer’s disease is a neurodegenerative disorder associated with progressive loss of neurons. It is the most common cause of dementia in older age. It develops over many years, producing irreversible brain changes and potentially leading to loss of independent functioning. The course of the disease may be delayed through early diagnosis and prompt initiation of treatment that improves quality of life. Early stages are often unrecognized; symptoms emerge slowly and progressively interfere with daily activities. Early signs may be difficult to verify because episodes of forgetfulness can also occur in younger individuals. Disease progression varies among patients; therefore, attention should be paid to atypical behaviors in older adults.

GHK-Cu in Alzheimer’s Disease Prevention

Through its functional profile, NL-GHK-Cu acts as a peptidomimetic inhibitor. It prevents the formation of toxic Aβ oligomers, fibrillar aggregates, and DNA damage. It is therefore a potential therapeutic candidate for attenuating the multifaceted Aβ toxicity observed in Alzheimer’s disease.

Moreover, among compounds with protective effects that may reduce oxidative damage are certain neurotrophic factors, such as brain-derived neurotrophic factor (BDNF). NL-GHK-Cu increases the production of neurotrophic factors. The peptide also stimulates the growth of cultured nerves, and nerve stumps placed within a collagen tube impregnated with NL-GHK-Cu show increased production of nerve growth factor. Neurotrophins NT-3 and NT-4 increase under the peptide’s influence, while accelerated cell migration into the collagen tube promotes regeneration of nerve fibers. In addition, NL-GHK-Cu increases axon numbers and stimulates Schwann cell proliferation.

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