Protein kinase C (PKC) is a diverse enzyme family crucial for cell signalling in various organs. Its dysregulation is linked to numerous diseases, including cancer, cardiovascular disorders, and neurological problems. In the brain, PKC plays pivotal roles in synaptic plasticity, learning, memory, and neuronal survival. Specifically, PKC’s involvement in Alzheimer’s Disease (AD) pathogenesis is of significant interest. The dysregulation of PKC signalling has been linked to neurological disorders, including AD. This review elucidates PKC’s pivotal role in neurological health, particularly its implications in AD pathogenesis and chronic alcohol addiction. AD, characterised by neurodegeneration, implicates PKC dysregulation in synaptic dysfunction and cognitive decline. Conversely, chronic alcohol consumption elicits neural adaptations intertwined with PKC signalling, exacerbating addictive behaviours. By unravelling PKC’s involvement in these afflictions, potential therapeutic avenues emerge, offering promise for ameliorating their debilitating effects. This review navigates the complex interplay between PKC, AD pathology, and alcohol addiction, illuminating pathways for future neurotherapeutic interventions.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. Recent findings suggest that long-term and heavy alcohol consumption can aggravate several pathological processes associated with AD, whereas the impact of light or moderate consumption remains uncertain. Excessive alcohol exposure impairs the structure and function of key brain regions involved in cognition, particularly the hippocampus, prefrontal cortex, amygdala, cerebellum, Basolateral amygdala (BLA), and hypothalamus. Several studies indicate that chronic alcohol consumption affects the brain by multiple mechanisms like increased oxidative stress, microglial activation, neuroinflammation, microtubule instability, tau hyperphosphorylation, and modified amyloid-β turnover. Disruption of cholinergic transmission further contributes to memory deficits and neuronal susceptibility. These alcohol-related alterations closely resemble core features of AD pathology and may accelerate disease progression. Although some epidemiological studies report the potential benefits of low alcohol intake, their interpretation is limited by inconsistent definitions of drinking patterns and the influence of confounding variables. Overall, current evidence supports a dose-dependent relationship in which alcoholism increases vulnerability to AD-related neurodegeneration. Reducing harmful alcohol use may therefore represent a practical approach to lowering long-term dementia risk. This review summarizes the current mechanisms of alcohol induced neuronal damage across different brain regions. Prolonged alcohol consumption accelerates cerebral aging by enhancing oxidative stress, neuroinflammation, disrupting tau protein degradations, and other neuronal damages that intersect with the pathogenesis of AD.