## 5 Pharmacologic Impact of Exosomes on the Treatment of Metabolic Diseases  
Recent research shows the potential of exosomes as innovative therapeutic agents across various fields of medicine. Alzheimer's disease (AD) is the leading neurodegenerative disease affecting millions globally, and there is compelling evidence that exosomes play a vital role in its progression and potential treatment. Exosomes may act as purifiers of A\(\beta\), helping to remove these proteins and potentially reducing amyloid plaque formation [78; 91]. In blood samples from AD patients, the levels of total tau, p-T181-Tau, p-S396-Tau, and A\(\beta\)1-42 proteins in neuron-derived exosomes (NDEs) were significantly elevated in preclinical individuals up to 10 years before being diagnosed with AD. Moreover, exosomes-derived A\(\beta\)1-42 levels from non-symptomatic to AD they can be a potential disease progression biomarker [79; 92]. Moreover, these pathological descriptions may be extended to other diseases in which amyloid formation is a fingerprint, such as T2 DM, with hIAPP amyloid formation [57; 65]. On the other hand, using exosomes for cardioprotection has been characterized. Interestingly, miR-21 exerts cardioprotective effects via the PTEN/Akt signaling pathway; miR-21 and its derivative miR-21-5p, found in exosomes from mesenchymal cells, play a crucial role in angiogenesis and significantly enhance the recovery of myocardial function, possibly through the conversion of macrophages to an M2 phenotype [90; 93]. Studies showed that purified exosomes from the plasma of rats undergoing remote ischemic conditioning reduce infarct size in an ischemia-reperfusion (I/R) injury model [94]. At the same time, those from exercising rats also provide protective effects against such injuries [95]. Evidence shows that exosomes from adipose tissue mesenchymal stem cells effectively reduce necrosis and apoptosis in ischemia/reperfusion models by activating the Wnt/\(\beta\)-catenin signaling pathway [96]. Exosomes from adipose tissue, bone marrow, and umbilical cord also decrease apoptosis and promote angiogenesis after myocardial infarction, underscoring their therapeutic potential [81; 82; 96; 97]. Exosomes significantly influence metabolism, particularly in obesity, T2 DM, insulin resistance, and nonalcoholic steatohepatitis (NASH) these metabolic disorders [83; 98]. Clinicaltrials.gov ([[https://clinicaltrials.gov/portal](https://clinicaltrials.gov/portal)]([https://clinicaltrials.gov/portal](https://clinicaltrials.gov/portal))) lists 133 clinical trials at various stages that are directly or indirectly connected to exosomes. Of these, 55 trials utilize these nanostructures in diverse evaluations, with the majority focusing on cancer-related applications [84; 99]. Therefore, the following examples represent the basis for identifying targets that can help treat metabolic diseases. Exosomes derived from obese human adipose tissue show differential of several miRNAs that can influence insulin sensitivity [85; 100]. Kranendonk et al. studied exosomes from the adipose tissue of obese mice and humans, showing that these exosomes promote insulin resistance by decreasing Akt phosphorylation and glucose uptake microRNAs (miRNA) from tissue of obese patients, with miR-141-3p highlighted as a key factor in inducing insulin resistance [92; 101]. Demonstrated that adipocyte-secreted exosomes with miR-34a exert effects such as inflammation, glucose tolerance, and insulin resistance [92; 101]. miR34a has been shown to be upregulated in visceral fat of obese subjects, and miR-34a KO mice displayed protection against obesity-related glucose intolerance and insulin [92; 101]. Moreover, miR-34a-KO mice exhibited reduced overall adipose tissue macrophage (ATM) levels, with fewerM1-like ATMs and more M2-like ATMs. This highlights a promising mechanism through which this miRNA regulates insulin sensitivity. In another report, miR-34a levels in visceral fat were associated with insulin resistance in obese subjects.