Abstract: Owing to the increasing life expectancy, the prevalence of age-dependent neurodegenerative diseases will exert an enormous toll on our aging population, their caregivers and the healthcare system. It is anticipated that numbers of patients suffering from diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and other neurodegenerative diseases are poised to increase markedly over the next few decades. Therefore, discovering treatments that mitigate the deleterious effects of these diseases is imperative. The common feature of neurodegenerative diseases is the loss of neurons, due to the accumulation of abnormal protein aggregates, which eventually cause dysfunction and death of neurons (Wareham et al., 2022). Stem cell niches are present in the adult brain, but the majority of neurogenesis takes place before adulthood, meaning that the terminally differentiated neurons, lost to neurodegenerative diseases, are unlikely to be replaced under normal physiological conditions. The loss of functional neurons will lead to permanent disability for patients. To date, the drug discovery effort for treating individual neurodegenerative diseases including AD, PD, and Huntington’s disease (HD) has been enormous, but the therapeutic strategy for preventing neuron loss in multiple neurodegenerative diseases is scarce.  In this perspective, we will discuss a recently discovered small peptide (Fan et al., 2019), named CX3CL1-ICD, which is derived from the intracellular domain of CX3CL1, for its translational potential through both enhancing neurogenesis and reducing neuronal apoptosis in neurodegenerative diseases.