The monoaminergic systems of the brainstem, including the locus coeruleus-noradrenergic system, are involved in several central processing due to their extensive projections. Any damage to these systems will lead to a wide range of nervous system disorders. Locus coeruleus nucleus, as the main source of noradrenaline in the mammalian brain is the first CNS modulatory system, which has been described in terms of anatomy and biochemistry. This nucleus, through noradrenaline, exerts a series of stimulatory and inhibitory effects on its target areas. Over the past few decades, locus coeruleus damage has been identified as a reason and a common factor in some diseases of the nervous system, including neurodegenerative diseases. In addition, these diseases are likely to be different manifestations of a common pathophysiological process, namely locus coeruleus damage. Attention to the role of the locus coeruleus nucleus as an intervening factor in the pathobiology of these diseases can also lead us to the role of this nucleus as a potential diagnostic and therapeutic target, especially in diseases such as Parkinson’s and Alzheimer’s diseases. The reason for the high vulnerability of locus coeruleus neurons, as well as their sensitivity to damage compared to other areas of the brain are unclear but it seems that specific anatomical and blood supply features, tau protein phosphorylation, need to high energy levels, environmental pollutions, and stress are among the effective factors, which they will be described in this review article.