| 1. |
|
|
| 2. |
|
|
| 3. |
- Patthy, A, et al.
(författare)
-
Neuropathology of the Brainstem to Mechanistically Understand and to Treat Alzheimer's Disease
- 2021
-
Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 10:8
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a devastating neurodegenerative disorder as yet without effective therapy. Symptoms of this disorder typically reflect cortical malfunction with local neurohistopathology, which biased investigators to search for focal triggers and molecular mechanisms. Cortex, however, receives massive afferents from caudal brain structures, which do not only convey specific information but powerfully tune ensemble activity. Moreover, there is evidence that the start of AD is subcortical. The brainstem harbors monoamine systems, which establish a dense innervation in both allo- and neocortex. Monoaminergic synapses can co-release neuropeptides either by precisely terminating on cortical neurons or, when being “en passant”, can instigate local volume transmission. Especially due to its early damage, malfunction of the ascending monoaminergic system emerges as an early sign and possible trigger of AD. This review summarizes the involvement and cascaded impairment of brainstem monoaminergic neurons in AD and discusses cellular mechanisms that lead to their dysfunction. We highlight the significance and therapeutic challenges of transmitter co-release in ascending activating system, describe the role and changes of local connections and distant afferents of brainstem nuclei in AD, and summon the rapidly increasing diagnostic window during the last few years.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Hanics, J, et al.
(författare)
-
Secretagogin-dependent matrix metalloprotease-2 release from neurons regulates neuroblast migration
- 2017
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 114:10, s. E2006-E2015
-
Tidskriftsartikel (refereegranskat)abstract
- Persisting proliferative capacity and regeneration in the adult brain are confined to a minority of regions. In the murine brain, the olfactory system is supplied by thousands of newly born neuroblasts daily to support sensory plasticity. Here, we reveal a neuronal scaffold that resides within and alongside this migratory route [termed the “rostral migratory stream” (RMS)] to guide forward migration of newly born neuroblasts. These neurons can externalize the enzyme matrix metalloprotease-2 to loosen the extracellular matrix, thus producing permissive corridors for migrating neuroblasts. This mechanism is likely phylogenetically conserved because it exists in the RMS equivalent in human fetal brains. This inducible mechanism might be pharmacologically targeted for therapeutic benefit.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
