Recent progress in the studies concerning the central nervous system (CNS) functional biology led to identification of regenerative potential in different pathophysiological conditions. Neurogenesis appears to be a complex process involving interaction of many endogenous bioactive factors. Their local biosynthesis and spatial distribution in neurogenic niches determine restrictive conditions to support this process in the brain. Especially, the secretory activity and structural integrity of nervous tissue microenvironment are responsible for efficiency and character of the biochemical processes that occur in this tissue. Proteins, which are involved in autocrine and paracrine regulation of nervous tissue activity in physiological/pathological conditions are defined as a neurotrophic factors (NTs). Neurotrophins possess strong neuroprotective properties and determine neuronal homeostasis inducing neural stem/progenitor cells (NSC/NPC) proliferation, migration and differentiation via specific/non-specific receptors interactions (TrkA, TrkB, TrkC, NGFRp75, RET). Therefore, the detailed aspects of signal transduction triggered by Trk, NGFRp75 and RET receptors, as a very complex and precise axis of CNS regulation, was extensively described in this study. Elucidation of signal transduction pattern in nervous tissue through the mediation of the above-mentioned receptors in distinct neurodegererative disorders in humans may facilitate preparation of background for novel therapeutic strategies.