| 1. |
- Li, Xuexin, et al.
(författare)
-
The anti-leprosy drug clofazimine reduces polyQ toxicity through activation of PPARγ
- 2024
-
Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 103
-
Tidskriftsartikel (refereegranskat)abstract
- Background: PolyQ diseases are autosomal dominant neurodegenerative disorders caused by the expansion of CAG repeats. While of slow progression, these diseases are ultimately fatal and lack effective therapies.Methods: A high-throughput chemical screen was conducted to identify drugs that lower the toxicity of a protein containing the fi rst exon of Huntington's disease (HD) protein huntingtin (HTT) harbouring 94 glutamines (Htt-Q94). 94 ). Candidate drugs were tested in a wide range of in vitro and in vivo models of polyQ toxicity.Findings: The chemical screen identified fi ed the anti-leprosy drug clofazimine as a hit, which was subsequently validated in several in vitro models. Computational analyses of transcriptional signatures revealed that the effect of clofazimine was due to the stimulation of mitochondrial biogenesis by peroxisome proliferator-activated receptor gamma (PPARγ). In agreement with this, clofazimine rescued mitochondrial dysfunction triggered by Htt-Q94 expression. Importantly, clofazimine also limited polyQ toxicity in developing zebrafish fish and neuron-specific worm models of polyQ disease.Interpretation: Our results support the potential of repurposing the antimicrobial drug clofazimine for the treatment of polyQ diseases.
|
|
| 2. |
- Sramkó, Bendegúz, et al.
(författare)
-
The Wisdom in Teeth : Neuronal Differentiation of Dental Pulp Cells
- 2023
-
Ingår i: Cellular Reprogramming. - : Mary Ann Liebert Inc. - 2152-4971 .- 2152-4998. ; 25:1, s. 32-44
-
Forskningsöversikt (refereegranskat)abstract
- Mesenchymal stem/stromal cells (MSCs) are found in almost all postnatal organs. Under appropriate environmental cues, multipotency enables MSCs to serve as progenitors for several lineage-specific, differentiated cell types. In vitro expansion and differentiation of MSCs give the opportunity to obtain hardly available somatic cells, such as neurons. The neurogenic potential of MSCs makes them a promising, autologous source to restore damaged tissue and as such, they have received much attention in the field of regenerative medicine. Several stem cell pool candidates have been studied thus far, but only a few of them showed neurogenic differentiation potential. Due to their embryonic ontology, stem cells residing in the stroma of the dental pulp chamber are an exciting source for in vitro neural cell differentiation. In this study, we review the key properties of dental pulp stem cells (DPSCs), with a particular focus on their neurogenic potential. Moreover, we summarize the various presently available methods used for neural differentiation of human DPSCs also emphasizing the difficulties in reproducibly high production of such cells. We postulate that because DPSCs are stem cells with very close ontology to neurogenic lineages, they may serve as excellent targets for neuronal differentiation in vitro and even for direct reprogramming.
|
|
