Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) play crucial roles in various physiological and pathological processes. MMPs are zinc-dependent endopeptidases that degrade the extracellular matrix (ECM), while TIMPs inhibit MMP activity. The balance between MMPs and TIMPs is essential for maintaining tissue homeostasis. Abnormal regulation of these enzymes is associated with several human diseases, including diabetes, neurodegenerative disorders, and cancer. **MMPs and TIMPs in Normal Physiological Conditions:** MMPs are involved in embryonic development, angiogenesis, and wound healing. They degrade specific ECM components, such as collagen and elastin. TIMPs, on the other hand, regulate MMP activity by forming reversible complexes with MMPs, thereby controlling ECM turnover and tissue remodeling. **Regulation of MMPs and TIMPs:** MMPs are regulated at multiple levels, including transcription, activation, interaction with ECM components, and inhibition by TIMPs. TIMPs have specific inhibitory profiles and can also interact with MMP proforms non-invasively. The expression and activity of MMPs and TIMPs are influenced by various factors, including cytokines, growth factors, and chemokines. **MMPs and TIMPs in Human Diseases:** - **Diabetes Mellitus:** Abnormal regulation of MMPs and TIMPs is linked to diabetic complications, such as nephropathy, neuropathy, and retinopathy. MMP-2, MMP-9, and TIMP-4 are particularly important biomarkers. - **Wound Healing:** MMPs and TIMPs are essential for wound healing, influencing cell migration, proliferation, and ECM remodeling. In diabetic patients, the hypoxic and inflammatory environment exacerbates wound healing issues. - **Renal Pathologies:** MMPs and TIMPs are involved in the progression of renal diseases, including acute kidney injury, glomerulosclerosis, and diabetic nephropathy. TIMP-1 is a significant predictor of fibrosis. - **Neurodegenerative Diseases:** MMPs and TIMPs contribute to the pathogenesis of multiple sclerosis (MS), Parkinson's disease (PD), and Alzheimer's disease (AD). In MS, the imbalance of MMPs and TIMPs leads to blood-brain barrier breakdown and neuronal damage. In PD, MMP overexpression contributes to dopaminergic neuron loss. In AD, MMPs degrade APP, leading to the formation of amyloid plaques and neurofibrillary tangles. **Current Strategies:** The abnormal regulation of MMPs and TIMPs in diseases has led to the development of MMP inhibitors as potential therapeutic targets. These inhibitors aim to modulate MMP activity and improve disease outcomes.Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) play crucial roles in various physiological and pathological processes. MMPs are zinc-dependent endopeptidases that degrade the extracellular matrix (ECM), while TIMPs inhibit MMP activity. The balance between MMPs and TIMPs is essential for maintaining tissue homeostasis. Abnormal regulation of these enzymes is associated with several human diseases, including diabetes, neurodegenerative disorders, and cancer. **MMPs and TIMPs in Normal Physiological Conditions:** MMPs are involved in embryonic development, angiogenesis, and wound healing. They degrade specific ECM components, such as collagen and elastin. TIMPs, on the other hand, regulate MMP activity by forming reversible complexes with MMPs, thereby controlling ECM turnover and tissue remodeling. **Regulation of MMPs and TIMPs:** MMPs are regulated at multiple levels, including transcription, activation, interaction with ECM components, and inhibition by TIMPs. TIMPs have specific inhibitory profiles and can also interact with MMP proforms non-invasively. The expression and activity of MMPs and TIMPs are influenced by various factors, including cytokines, growth factors, and chemokines. **MMPs and TIMPs in Human Diseases:** - **Diabetes Mellitus:** Abnormal regulation of MMPs and TIMPs is linked to diabetic complications, such as nephropathy, neuropathy, and retinopathy. MMP-2, MMP-9, and TIMP-4 are particularly important biomarkers. - **Wound Healing:** MMPs and TIMPs are essential for wound healing, influencing cell migration, proliferation, and ECM remodeling. In diabetic patients, the hypoxic and inflammatory environment exacerbates wound healing issues. - **Renal Pathologies:** MMPs and TIMPs are involved in the progression of renal diseases, including acute kidney injury, glomerulosclerosis, and diabetic nephropathy. TIMP-1 is a significant predictor of fibrosis. - **Neurodegenerative Diseases:** MMPs and TIMPs contribute to the pathogenesis of multiple sclerosis (MS), Parkinson's disease (PD), and Alzheimer's disease (AD). In MS, the imbalance of MMPs and TIMPs leads to blood-brain barrier breakdown and neuronal damage. In PD, MMP overexpression contributes to dopaminergic neuron loss. In AD, MMPs degrade APP, leading to the formation of amyloid plaques and neurofibrillary tangles. **Current Strategies:** The abnormal regulation of MMPs and TIMPs in diseases has led to the development of MMP inhibitors as potential therapeutic targets. These inhibitors aim to modulate MMP activity and improve disease outcomes.