ORCID Profile
0000-0001-9645-0572
Current Organisations
University of Nottingham
,
Shaqra University
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Publisher: Wiley
Date: 21-05-2023
DOI: 10.1111/JCMM.17784
Abstract: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). Genetic predisposition and immune dysfunction are involved in the pathogenesis of PD. Notably, peripheral inflammatory disorders and neuroinflammation are associated with PD neuropathology. Type 2 diabetes mellitus (T2DM) is associated with inflammatory disorders due to hyperglycaemia‐induced oxidative stress and the release of pro‐inflammatory cytokines. Particularly, insulin resistance (IR) in T2DM promotes the degeneration of dopaminergic neurons in the substantia nigra (SN). Thus, T2DM‐induced inflammatory disorders predispose to the development and progression of PD, and their targeting may reduce PD risk in T2DM. Therefore, this narrative review aims to find the potential link between T2DM and PD by investigating the role of inflammatory signalling pathways, mainly the nuclear factor kappa B (NF‐κB) and the nod‐like receptor pyrin 3 (NLRP3) inflammasome. NF‐κB is implicated in the pathogenesis of T2DM, and activation of NF‐κB with induction of neuronal apoptosis was also confirmed in PD patients. Systemic activation of NLRP3 inflammasome promotes the accumulation of α‐synuclein and degeneration of dopaminergic neurons in the SN. Increasing α‐synuclein in PD patients enhances NLRP3 inflammasome activation and the release of interleukin (IL)‐1β followed by the development of systemic inflammation and neuroinflammation. In conclusion, activation of the NF‐κB/NLRP3 inflammasome axis in T2DM patients could be the causal pathway in the development of PD. The inflammatory mechanisms triggered by activated NLRP3 inflammasome lead to pancreatic β‐cell dysfunction and the development of T2DM. Therefore, attenuation of inflammatory changes by inhibiting the NF‐κB/NLRP3 inflammasome axis in the early T2DM may reduce future PD risk.
Publisher: Springer Science and Business Media LLC
Date: 13-05-2023
DOI: 10.1186/S13098-023-01082-1
Abstract: Human Islet amyloid polypeptide (hIAPP) from pancreatic β cells in the islet of Langerhans has different physiological functions including inhibiting the release of insulin and glucagon. Type 2 diabetes mellitus (T2DM) is an endocrine disorder due to relative insulin insufficiency and insulin resistance (IR) is associated with increased circulating hIAPP. Remarkably, hIAPP has structural similarity with amyloid beta (Aβ) and can engage in the pathogenesis of T2DM and Alzheimer’s disease (AD). Therefore, the present review aimed to elucidate how hIAPP acts as a link between T2DM and AD. IR, aging and low β cell mass increase expression of hIAPP which binds cell membrane leading to the aberrant release of Ca 2+ and activation of the proteolytic enzymes leading to a series of events causing loss of β cells. Peripheral hIAPP plays a major role in the pathogenesis of AD, and high circulating hIAPP level increase AD risk in T2DM patients. However, there is no hard evidence for the role of brain-derived hIAPP in the pathogenesis of AD. Nevertheless, oxidative stress, mitochondrial dysfunction, chaperon-mediated autophagy, heparan sulfate proteoglycan (HSPG), immune response, and zinc homeostasis in T2DM could be the possible mechanisms for the induction of the aggregation of hIAPP which increase AD risk. In conclusion, increasing hIAPP circulating levels in T2DM patients predispose them to the development and progression of AD. Dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists attenuate AD in T2DM by inhibiting expression and deposition of hIAP.
Publisher: Elsevier BV
Date: 2023
DOI: 10.1016/J.IJBIOMAC.2022.10.168
Abstract: Diabetic retinopathy (DR) is one of the chronic complications of diabetes. It includes retinal blood vessels' damage. If untreated, it leads to loss of vision. The existing treatment strategies for DR are expensive, invasive, and need expertise during administration. Hence, there is a need to develop a non-invasive topical formulation that can penetrate deep to the posterior segment of retina and treat the damaged retinal vessels. In addition, it should also provide sustained release. In recent years, novel drug delivery systems (NDDS) have been explored for treating DR and found successful. In this study, chitosan (CS) modified 5-Fluorouracil Nanostructured Lipid Carriers (CS-5-FU-NLCs) were prepared by modified melt emulsification-ultrasonication method and optimized by Box-Behnken Design. The size, polydispersity index, zeta potential and entrapment efficiency of CS-5-FU-NLCs were 163.2 ± 2.3 nm, 0.28 ± 1.52, 21.4 ± 0.5 mV and 85.0 ± 0.2 %, respectively. The in vitro drug release and ex vivo permeation study confirmed higher and sustained drug release in CS-5-FU-NLCs as compared to 5-FU solution. HET-CAM Model ensured the non-irritant nature of CS-5-FU-NLCs. In vivo ocular studies of CS-5-FU-NLCs confirmed antiangiogenic effect of 5-FU by CAM model and diabetic retinopathy induced rat model, indicating successful delivery of 5-FU to the retina.
Publisher: Wiley
Date: 11-04-2023
DOI: 10.1111/PIM.12982
Abstract: Helminths are metazoan parasites affecting about one third of the worldwide population. Chronic helminth infections (CHIs) confer immunological tolerance to harmless and self‐antigens mediated by regulatory T cells (Treg) that are up‐regulated. In coronavirus disease 2019 (COVID‐19), abnormal adaptive immune response and unrestrained innate immune response could result in local and systemic immune‐mediated tissue damage. COVID‐19 and CHIs establish complicated immune interactions due to SARS‐CoV‐2‐induced immunological stimulation and CHIs‐induced immunological tolerance. However, COVID‐19 severity in patients with CHIs is mild, as immuno‐suppressive anti‐inflammatory cytokines counterbalance the risk of cytokine storm. Here, an overview of the interplay between helminths and COVID‐19 severity is given. CHIs through helminth‐derived molecules may suppress SARS‐CoV‐2 entry and associated hyperinflammation through attenuation of the TLR4/NF‐kB signalling pathway. In addition, CHIs may reduce the COVID‐19 severity by reducing the SARS‐CoV‐2 entry points at ACE2/DPP4/CD147 axis in the initial phase and immunomodulation in the late phase of the disease by suppressing TLR4/NF‐kB signalling pathway.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Mohammed Alrouji.