ABSTRACT:
Neuritogenesis or neuritic outgrowth is a fundamental cellular differentiation process for formation of nes neurons. Recent reports have indicated importance of this process in neuroregeneration and repair of damaged neurun. Neurotrophic and Neuritogenic substances, which repair damaged neurons through stimulation of neuritic outgrowth, may be important for restoration and readjustment of normal neuronal functions of the damaged neurons. Neurotrophins namely. Nerve Growth Factor (NGF). Brain Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT-3) and Neurotrophin-4 (NT- 4), stimulate neuritogenesis through regulation of neural survival, development, function, and plasticity. The neurotrophins may have potential application in treatment of neuronal injuries and neurodegenerative diseases. However, inadequate a negligible penetration through blood brain barrier and susceptibility to degradation by the peripheral proteases prevent therapeutic application of endogenous peptide neurotrophins. The bioactive small molecules with neurotrophic nd neuritogenic actions hold great promise as therapeutic agents for treatment of neurodegenerative diseases and neurt injuries by virtue of their ahility to stimulate neuritic outgrowth. Use of natural products eliciting neuritogenic activity ak or in combination with neurotrophic substances is currently being focused as an important approach. In addition to thik te evidences also shows that compounds capable of enhancing the action of neurotrophic factors to stimulate neunte ougo may be useful in the treatment of neurological disorders such as Parkinson's disease (PD) and Alzheimer's discase r Hence, identification of neuritogenic & neurotrophic molecules from natural sources may provide important anig ku fot activation of neuroregeneration in various forms of neuronal injuries. Screening of natural compounds lihran stimulation of neuritic outgrowth in in vitro cell-culture models have identified sseveral neurotrophic and neuritgee product substances. Neurotrophic tyrosine kinase receptor type I Trk-A) is a membrane-bound high affinity nerve growth factor receptor that, upon neurotrophin binding, phosphorylates itself (autophosphorylation) and members of the MAPY pathway. Activation of Trk-A triggers a signal transductions cascade, which leads to cell differentiation and may play a mle in specifying sensory neuron subtype. A transgenic cell line overexpressing TrkA receptor functions have pruvide important tool for large scale screening of natural products libraries. Focused screening of a library of harmala alkaleds selected cannahis constituents and other natural products has identified new natural products leads, which produced significant activation of NGF-stimulated neuritic outgrowth. Further interrogations of the lead natural products through TrkA-A associated signal transduction pathways; histone deacetylases and cell-cycle associated functions have provided useful clues reparding mechanism for neuritogenic action. Similar approach has also been applied for screening a library of extracts prepared from the botanicals, which are traditionally known to improve brain functions, learning, memory and other neurological disorders.