This review says that humanin and related tiny proteins from mitochondria look promising for protecting brain cells in diseases like Alzheimer’s, Parkinson’s, and Huntington’s, but the science is still early and we don’t yet know exactly how they work or the best way to give them to people.

Mitochondrial-derived peptides (MDPs), including humanin, MOTS-c, and small humanin-like peptides (SHLPs), have emerged as promising therapeutic candidates for neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). This review systematically evaluates current literature retrieved from databases including PubMed, Scopus, and Web of Science using keywords such as "mitochondrial-derived peptides," "neurodegeneration," "humanin," "MOTS-c," and "SHLPs." Studies were included based on their relevance to mitochondrial function, oxidative stress, neuroprotection, and anti-inflammatory mechanisms in AD, PD, and HD models. Despite growing interest, current research remains limited in understanding the precise molecular pathways. Our review highlights their role in mitigating disease-specific pathologies such as Amyloid-beta (Aβ) toxicity in AD, dopaminergic neuron loss in PD, and mutant huntingtin aggregation in HD while also emphasizing their potential to attenuate oxidative stress and neuroinflammation. By identifying critical knowledge gaps, particularly in the areas of molecular mechanisms of MDPs in neuroprotection, targeted delivery, and clinical translation, this review provides a comprehensive framework to guide future investigations.