Biology subjects

Amin, A.

Publications and source records attributed to Amin, A..

22 records · Page 2Linked to original sources

bioRxiv2021

Amelioration of L-DOPA-induced dyskinesia with vitamin D3 in Parkinsonian mice model

L-DOPA Induced Dyskinesia (LID) is associated with prolonged L-DOPA therapy. Vitamin-D receptor modulation improves motor-cognitive deficit in experimental LID Parkinsonism. Therefore, in this study, we investigated the mechanism underlying the anti-dyskinetic potential of Vitamin D3 (VD3). Dyskinesia was induced by chronic L-DOPA administration in 6-OHDA lesioned male C57BL6 mice. The experimental groups (Dyskinesia, Dyskinesia/VD3, and Dyskinesia/Amantadine) and controls were challenged with L-DOPA to determine the abnormal involuntary movements (AIMs) score during 14 days of VD3 (30 mg/kg) or Amantadine (40 mg/kg) treatment. Global behavioral Axial, Limb & Orolingual (ALO) AIMs were scored for 1 min at every 20 mins interval, over a duration of 100 mins on days 1,3,7,11 and 14 of treatment. Thereafter, brain samples were collected and processed for immunoblotting to assess striatal expression of tyrosine hydroxylase (TH), monoamine oxidase (MAO), cathecol-o-methyl transferase (COMT), dopamine decarboxylase (DDC), CD11b, BAX, P47phox, and IL-1{beta}. VD3 significantly attenuated ALO AIMs only on days 11 & 14, with maximal reduction of 32.7% compared with dyskinetic mice but had no effect on days 1, 3 & 7, while amantadine decreased AIMs all through days 1 to 14 with maximal reduction of 64.5%. TH and MAO-B expression were not significantly different across the groups. DDC was significantly suppressed in dyskinetic mice vs control (p<0.001) but remained unchanged in VD3 mice vs dyskinetic mice. COMT was upregulated in the dyskinetic group vs control (p<0.01) and attenuated in VD3 mice (p<0.05) compared to the dyskinetic group. Interestingly, VD3 inhibited significantly (p<0.01) oxidative stress (p47phox), apoptosis (BAX), inflammation (IL-1{beta}), and microglial activation (CD11b) in dyskinetic mice. Overall, we find that the anti-dyskinetic effects of VD3 is associated with modulation of striatal oxidative stress, microglial responses, inflammation, and apoptotic signaling. Impact statementThere are evidences showing that VD3 supplementation improves motor disorders, including Parkinsons disease. We hypothesized that VD3 could improve LID, an abnormal involuntary movement that results from prolonged L-DOPA therapy in the management of PD. We have demonstrated the novel anti-dyskinetic effect of VD3 and associated mechanistic factors in a mouse model of L-DOPA Induced Dyskinesia (LID), which identifies promising targets for dyskinesia therapy.

neuroscience↗

bioRxiv2020

20 years of African Neuroscience: Waking a sleeping giant

Understanding the function and dysfunction of the brain remains one of the key challenges of our time. However, an overwhelming majority of brain research is carried out in the Global North, by a minority of well-funded and intimately interconnected labs. In contrast, with an estimated one neuroscientist per million people in Africa, news about neuroscience research from the Global South remains sparse. Clearly, devising new policies to boost Africa’s neuroscience landscape is imperative. However, the policy must be based on accurate data, which is largely lacking. Such data must reflect the extreme heterogeneity of research outputs across the continent’s 54 countries distributed over an area larger than USA, Europe and China combined. Here, we analysed all of Africa’s Neuroscience output over the past 21 years. Uniquely, we individually verified in each of 12,326 publications that the work was indeed performed in Africa and led by African-based researchers. This step is critical: previous estimates grossly inflated figures, because many of Africa’s high-visibility publications are in fact the result of internationally led collaborations, with most work done outside of Africa. The remaining number of African-led Neuroscience publications was 5,219, on average only ~5 per country and year. From here, we extracted metrics such as the journal and citations, as well as detailed information on funding, international collaborations and the techniques and model systems used. We link these metrics to demographic data and indicators of mobility and economy. For reference, we also extracted the same metrics from 220 randomly selected publications each from the UK, USA, Australia, Japan and Brazil. Our unique dataset allows us to gain accurate and in-depth information on the current state of African Neuroscience research, and to put it into a global context. This in turn allows us to make actionable recommendations on how African research might best be supported in the future.Competing Interest StatementThe authors have declared no competing interest.View Full Text

scientific communication and education↗

bioRxiv2020

Network and pathway expansion of genetic disease associations identifies successful drug targets

It is widely accepted that genetic evidence of disease association acts as a sound basis for the selection of drug targets for complex common diseases and that propagation of genetic evidence through gene or protein interaction networks can accurately infer novel disease associations at genes for which no direct genetic evidence can be observed. However, an empirical test of the utility of combining these beliefs for drug discovery has been lacking. In this study, we examine genetic associations arising from an analysis of 648 UK Biobank GWAS and evaluate whether targets identified as proxies of direct genetic hits are enriched for successful drug targets, as measured by historical clinical trial data. We find that protein networks formed from specific functional linkages such as protein complexes and ligand-receptor pairs are suitable for even naive guilt-by-association network propagation approaches. In addition, more sophisticated approaches applied to global protein-protein interaction networks and pathway databases, also successfully retrieve targets enriched for clinically successful drug targets. We conclude that network propagation of genetic evidence should be used for drug target identification.

genetics↗

bioRxiv2019

FOP plays a negative role in ciliogenesis and promotes cell cycle re-entry by facilitating primary cilia disassembly

Primary cilia are microtubule-based, antenna-like organelles, which are formed in G0 phase and resorbed as cells re-enter the cell cycle. It has been reported that the length of primary cilia can influence the timing of cell cycle progression. However, the molecular links between ciliogenesis and cell cycle progression are not clear. FOP (Fibroblast growth factor receptor 1 Oncogene Partner, also known as FGFR1OP) has been implicated in ciliogenesis. Here, we show that the expression of FOP during cell cycle exit and re-entry is negatively correlated with ciliogenesis. Knockdown of FOP promotes cilia elongation and suppresses timely cilia disassembly. In contrast, ectopic expression of FOP inhibits cilia growth. Moreover, pharmacological inhibition of actin polymerization with Cytochalasin D abrogates FOP-induced cilia disassembly, suggesting that FOP facilitates cilia disassembly by promoting actin cytoskeleton formation. Lastly, knockdown of FOP delays cell cycle re-entry of quiescent cells following serum re-stimulation, and this can be reversed by silencing IFT20 (intraflagellar transport 20), an intraflagellar transport protein essential for ciliogenesis. Collectively, these results suggest that FOP plays a negative role in ciliogenesis and can promote cell cycle re-entry by facilitating cilia disassembly.

cell biology↗