Demographic Analysis of the Sun Protective Behaviours and Skin Cancer Risk of Victorian Farmers.

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and constitutes the primary cause of cognitive impairment among the elderly population. With the ongoing demographic shift toward an aging society, the socioeconomic burden of AD is escalating at an unprecedented rate []. Clinically, AD manifests as progressive deterioration of cognitive function, neuropsychiatric symptoms, and a loss of independence in performing activities of daily living. The neuropathological hallmarks involve extracellular amyloid-β (Aβ) plaques and intraneuronal neurofibrillary tangles (NFTs) composed of hyper-phosphorylated tau (p-tau), which continue to serve as the gold-standard biomarkers for the disease []. Recently, emerging evidence implicates metabolic dysregulation, neuroinflammation, and epigenetic dysfunctions as critical drivers of AD pathogenesis [,]. Protein acylation, a critical protein post-translational modification (PTM), is integral to numerous physiological and pathological cellular processes, particularly those associated with neurodegenerative diseases, cancer, and metabolic disorders [,]. A significant number of acylations, notably novel lysine acylations such as protein lysine succinylation, propionylation, malonylation, crotonylation, butyrylation, 2-hydroxyisobutyrylation, β-hydroxybutyrylation, glutarylation, benzoylation, lactylation, and isonicotinylation, establish a direct connection between cellular metabolism and both epigenetic remodeling and protein functionality []. Novel acylations influence transcriptional programs by modifying chromatin architecture and DNA accessibility. Moreover, they affect protein stability, enzymic activity, protein–protein interactions, and subcellular localization through alterations in protein conformation [,, , , ]. Consequently, these acylations orchestrate energy metabolism, neuroinflammatory signaling, autophagy, and programmed cell death, all of which are critical contributors to AD pathology. In this review, we offer an extensive analysis of novel acylations, demonstrating the enzymatic processes and regulatory mechanisms. We further delineate the molecular significances of these acylations in the regulation of gene transcription and protein functionality. Moreover, by scrutinizing the regulatory mechanisms involved, this review explores the expanding role of novel protein acylations in AD, assesses their potential as biomarkers for early diagnosis and prognosis, and highlights emerging therapeutic strategies targeting disrupted acylation networks. We also propose future research directions to translate these insights into clinical applications, aiming to enhance our understanding of AD pathogenesis and foster the development of targeted interventions.