03922nam a22001457a 4500003000500000082000800005100001900013245010700032264003600139300001900175500345600194650003603650700003203686856005803718NUST  a610  aABID , ATTIAH   aMitochondrial Dysfunction in Psoriasis Examining Stress Pathways in Protective and Metabolic Tissues /  aIslamabad :bSMME NUST ,c2026.  a103p. ;c30cm.  aPsoriasis, a chronic immune-mediated skin disorder affecting approximately 2–3% of the
global population, has gained increasing recognition for its systemic effects. Emerging
evidence suggests a link between psoriasis-associated systemic inflammation and
neurodegenerative diseases such as dementia and Alzheimer’s disease. This research study
combined bioinformatics with experimental methods to examine the connection between
psoriasis-related inflammation and neurodegeneration via mitochondrial stress-signaling.
Protein-Protein interaction analysis of the target markers MAPT, APP, SIRT2, MAPK1 and
PRDX1 revealed that MAPK1 and PRDX1 are central interaction nodes in networks related to
neurodegeneration. Protein-ligand docking indicated that turmeric-derived compounds,
especially demethoxycurcumin, followed by quercetin, bisdemethoxycurcumin and curcumin,
had strong binding affinities whereas promising chamomile-derived ligands were
quercimeritrin, stigmasterol, rutin and oleanic acid. The functional enrichment analysis
investigated through STRING, SHINYGO, G-Profiler and ENRICHR pathway analysis showed
that redox regulation, inflammatory signaling, and synaptic plasticity pathways were coordinately involved in linking the selected markers. Moreover, SwissTarget Prediction Tool
and ChEMBL implied that the potential protein targets of synthesized turmeric-chamomile drug
formulation were primarily associated with Neuroactive ligand-receptor and GPCR signaling,
Serotonergic synapse, Calcium/cAMP signaling, MAPK/PI3K-AKT/ErbB/Notch pathways,
Nuclear and extra-nuclear estrogen receptor signaling, Oxidative stress/redox, Eicosanoid
and ω-3 PUFA metabolism, Alzheimer’s disease, IL-17/IL-6/IL-5 signaling, Oxytocin
signaling, and Gap junction/FoxO signaling to modulate the severity of psoriasis, AD and
mitochondrial dysfunction. Based on the promising in-silico analysis, we subsequently
performed in vivo experiments. Previously, using polymeric nanoparticle delivery systems, the
plant-derived compounds Curcuma longa and Matricaria recutita topical gel was tested in
BALB/c IMQ-induced psoriasis murine model. Water Morris and Y Maze Tests cognitive
behavioural and histological (H&E staining) assessments pinpointed that untreated psoriatic
mice exhibited significant cognitive deficits, supporting the skin–brain interaction hypothesis.
Obtaining these findings, we further investigated the molecular transcriptional analysis of
protective and metabolic tissues using RT-qPCR. Stress and neurodegeneration markers,
MAPT, APP, SIRT2, PRDX1, and MAPK were significantly upregulated in liver, eyes,
hippocampus, and cortex samples. Their expression was, however, decreased to control levels
using turmeric-chamomile gel. The nanoparticles encapsulated by drug formulation (TDN)
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showed relatively better therapeutic efficacy than free form drug (TD). Tissue specific
responses were also seen in skin tissues where SIRT2 and PRDX1 were downregulated in
diseased samples and later returned to normal levels following treatment. These results
underscore the importance of the skin–brain axis and potential molecular targets for therapeutic
strategies aimed at mitigating cognitive decline in patients with psoriasis.
Keywords: Psoriasis, Neurodegeneration, Alzheimer’s Disease, Mitochondrial Dysfunction,
Turmeric, Chamomile, Polymeric Nanoparticles, Neuroinflammation, Stress pathways, qRTPCR, In-silico analysis   aMS in Biomedical Sciences (BMS)  aSupervisor: Dr. Saima Zafar  u http://10.250.8.41:8080/xmlui/handle/123456789/57553