Roles of humanin and derivatives on the pathology of neurodegenerative diseases and cognition

• Published in: Biochimica et biophysica acta. General subjects Vol. 1866; no. 4; p. 130097
• Main Authors: Thiankhaw, Kitti, Chattipakorn, Kenneth, Chattipakorn, Siriporn C, Chattipakorn, Nipon
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2022
• Subjects: Alzheimer disease; Alzheimer Disease - metabolism; amyloid; Animals; Apoptosis Regulatory Proteins; Autophagy; Brain; Cognition; Dementia; Humanin; Humans; insulin; Intracellular Signaling Peptides and Proteins; Macular Degeneration; Mice; Mitochondria; Neurodegenerative Diseases; neuropathology; neurotransmitters; oxidative stress; Parkinson Disease; pathogenesis; Peptides; Reperfusion Injury; therapeutics; Brain; Mitochondria; Autophagy; Humanin; Dementia
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2022.130097

Alzheimer's disease (AD), Parkinson's disease (PD), and age-related macular degeneration (AMD) are common among neurodegenerative diseases, but investigations into novel therapeutic approaches are currently limited. Humanin (HN) is a mitochondrial-derived peptide found in brain tissues of patients with familial AD and has been increasingly investigated in AD and other neurodegenerative diseases. In this review, we summarize and discuss the effects of HN on the pathology of neurodegenerative diseases and cognition based on several studies from preclinical to clinical models. The association between cardiac ischemia-reperfusion (I/R) injury and brain are also included. Findings from in vitro studies and those involving mice provide the most fundamental information on the impact of HN and its potential association with clinical studies. HN plays a considerable role in countering the progression and neuropathology of AD. Inhibition and reduction of oxidative stress and neuroinflammation of the original amyloid hypothesis is the mainstay mechanism. Multiple intracellular mechanisms will be elucidated, including those involved in the anti-apoptotic signaling cascades, the insulin signaling pathway, and mitochondrial function, and especially autophagic activity. These beneficial roles are also found following cardiac I/R injury. Cognitive improvement was found to be related to maintenance of synaptic integrity and neurotransmitter modulation. Small humanin-like peptide 2 demonstrates the neuroprotective effects in PD and AMD via prevention of mitochondrial loss. Comprehensive knowledge of HN effects on cognition and neurodegenerative diseases emphasizes its potential to treat a viable disease, as it ameliorates the pathogenesis of the disease. [Display omitted] •Humanin and derivatives have been proposed for neurodegenerative treatment.•Anti- Aβ aggregation and P-tau attenuation is important mechanism in AD contexts.•Intracellular anti-apoptotic pathways are also demonstrated in preclinical models.•Reduced mitochondrial failure is another effect on neurodegeneration and cardiac I/R injury.•It provides a novel therapeutic intervention for AD, targeted to pathogenesis.