Abstract
Reinstalling the neurobiological circuits to effectively change the debilitating course of neurodegenerative diseases is of utmost importance. This reinstallation requires generation of new cells which are able to differentiate into specific types of neurons and modification of the local environment suitable for integration of these new neurons into the neuronal circuits. Allopregnanolone (APα) seems to be involved in both of these processes, and therefore, is a potential neurotrophic agent. Loss of dopamine neurons in the substantia nigra (SN) is one of the main pathological features of Parkinson’s and also in, at least, a subset of Alzheimer’s patients. Therefore, reinstallation of the dopamine neurons in nigrostriatal tract is of unique importance for these neurodegenerative diseases. However, for the neurogenic status and the roles of allopregnanolone in the nigrostriatal tract, the evidence is accumulating and debating. This review summarizes recent studies regarding the neurogenic status in the nigrostriatal tract. Furthermore, special attention is placed on evidence suggesting that reductions in allopregnenalone levels are one of the major pathological features in PD and AD. This evidence has also been confirmed in brains of mice that were lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or those bearing neurodegenerative mutations. Lastly, we highlight studies showing that allopregnanalone can augment the number of total cells and dopaminergic neurons via peripheral exogenous administration.
Highlights
Research data consistently suggests that a small molecule, the neurosteroid allopregnanolone (APα) capable of permeating the brain-blood-barrier, is a latent restorative therapeutic agent for reestablishing neuronal circuits in hippocampus and the nigrostrital tract
This review summarizes and highlights the current discoveries involving the generation of new neurons in the nigrostriatal tract and the therapeutic potential for the related neuronal disorders of APα
A reduction in the dopamine metabolite DOPAC was observed in the striatum of these mice (Perez et al, 2005). These findings suggested a close association between amyloid deposition and nigrostriatal pathology and suggest that altered familial AD-linked amyloid metabolism impairs, at least in part, the function of dopaminergic neurons
Summary
Research data consistently suggests that a small molecule, the neurosteroid allopregnanolone (APα) capable of permeating the brain-blood-barrier, is a latent restorative therapeutic agent for reestablishing neuronal circuits in hippocampus and the nigrostrital tract. Accumulated data indicated that APα increased the number of total cells, tyrosine hydroxylase (TH) positive cells, and newly formed (BrdU positive) TH expressing cells in the substantia nigra (SN), and improved the balance and coordination of 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mice, an animal model for Parkinson’s disease (PD; Adeosun et al, 2012).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
