Parkinson’s Disease (PD) is the second most common neurodegenerative disorder seen, especially in the elderly. Tremor, shaking, movement problems, and difficulty with balance and coordination are among the hallmarks, and dopaminergic neuronal loss in substantia nigra pars compacta of the brain and aggregation of intracellular protein α-synuclein are the pathological characterizations. Neuroinflammation has emerged as an involving mechanism at the initiation and development of PD. It is a complex network of interactions comprising immune and non-immune cells in addition to mediators of the immune response. Microglia, the resident macrophages in the CNS, take on the leading role in regulating neuroinflammation and maintaining homeostasis. Under normal physiological conditions, they exist as “homeostatic” but upon pathological stimuli, they switch to the “reactive state”. Pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes are used to classify microglial activity with each phenotype having its own markers and released mediators. When M1 microglia are persistent, they will contribute to various inflammatory diseases, including neurodegenerative diseases, such as PD. In this review, we focus on the role of microglia mediated neuroinflammation in PD and also signaling pathways, receptors, and mediators involved in the process, presenting the studies that associate microglia-mediated inflammation with PD. A better understanding of this complex network and interactions is important in seeking new therapies for PD and possibly other neurodegenerative diseases.

Celery (Apium graveolens L.), one of the numerous members of the Apiaceae family, has been traditionally used as food and medicine due to its nutraceutical properties. Nevertheless, understanding the neuroprotective effects of this species requires evaluation through different mechanisms relevant to Alzheimer’s disease (AD) treatment. This study explored the neuroprotective potential of ethanolic extracts of celery leaves. Liquid chromatography and mass spectrometry-based metabolomics analysis of the extract revealed the existence of a diverse array of secondary metabolites, including phenolic acids, hydroxycinnamic acid, flavonoids, flavonoid O-glycosides, flavonol, glycosides, and isoflavones. Celery extract protects human neuroblastoma SH-SY5Y cells against 15 µM amyloid-beta (Aβ_1–42) toxicity, enhancing their vitality from 67% to 81.74% at 100 µg/mL. The extract inhibited the enzymes associated with AD, including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), glycogen synthase kinase 3 beta (GSK3β), cyclooxygenase 1 (COX-1), and cyclooxygenase 2 (COX-2) with IC₅₀ values of 21.84, 61.27, 45.94, 34.1, and 52.2 µg/mL, respectively. In conclusion, celery leaf extract components may be potential therapeutic candidates for AD prevention and treatment.

Neuroinflammation in the pathogenesis of neurodegenerative diseases is still a subject of discussion, as it might be either the cause or the result of neurodegeneration. Misfolded or improperly aggregated α-synuclein in Parkinson’s Disease, can cause inflammatory responses, indicating a mechanistic relationship between α-synuclein pathology and neuroinflammation. The aim of this study was to investigate the role of DNA topoisomerase IIβ, the key player of DNA topology, in the neuroinflammation process in an age-dependent transgenic Parkinson’s Disease mouse model overexpressing the A53T mutant α-synuclein. In this study, transgenic and control mice were bred in three age groups as early (3 months), mid (8 months), and late (12 months) disease stages. Behavioral experiments were carried out to compare the age-related cognitive and motor coordination functions. Cytokine levels in the serum and protein expression levels in the dissected brain were analyzed by both western blot and immunofluorescence staining. A decline was observed in the cognitive and motor coordination functions depending on age. Disease-related markers at protein level appeared even in the early stage, and accordingly, a significant increase was observed in inflammatory markers and cytokine levels compared to control. DNA Topoisomerase IIβ and Nurr1 levels decreased in transgenic mice, especially more dramatically in the early stage. The combined effect of reduced Nurr1 and DNA Topoisomerase IIβ, along with increased inflammation, may provide a better understanding of the pathogenesis of Parkinson’s Disease at early-stage and requires for further investigation of the potential alterations in topo IIβ as an intervention strategy for this disease.

In recent times, chimeric antigen receptor (CAR)-T cell therapy has shown rapid advancements and gained clinical approval for use in cancer immunotherapy. CAR, a synthetic receptor integrated into autologous T cells, has yielded highly successful results in patients with leukemia. The significant potential of CAR-T cells has been validated through clinical trials in adult and pediatric cancer treatments. Our therapy developed specifically for CD19-specific Acute Lymphoblastic Leukemia (ALL) has shown promising results in in vitro and in vivo tests. To enhance the response against cancer, provide a bistimulatory effect, and increase stability, we designed two different CAR structures specific to CD19. These designs incorporate the CD28 and 41BB costimulatory domains. Through in vitro analysis, we evaluated the population ratios and cytotoxic activities of Central Memory T cells (TCM) and Stem Cell Memory T cells (TSCM) in CAR-T (CAR1928-T and CAR19BB-T) cells. Our initial design, CAR1928-T, produced an effective anti-tumor response. With our second design, CAR19BB-T, we not only achieved an anti-tumor effect but also conferred memory capabilities, leading to a comprehensive treatment approach. We demonstrated that CAR-T cells produced using Phytohemagglutinin (PHA) exhibited increased persistence in vitro and in vivo compared to anti-CD3 and anti-CD28 stimulation. The use of PHA to activate CAR19BB-T cells developed a long-lasting and effective CAR-T cell production method in vivo using cancerous animal models. CAR-T cell-treated mice survived tumor-free for up to 60 days, surpassing the survival of mice that received tumors only. Additionally, CAR19BB-T cell production with PHA remained stable over time. These results highlight a novel CAR-T cell production approach with a high-memory T cell profile capable of delaying or preventing cancer relapse. We optimized the method for the production of long-term and effective CAR-T cells and tested it in preclinical experiments. As a result, it was demonstrated that CAR-T cells generated with PHA, when administered as a co-stimulatory dose, can provide continuous proliferation and long-term persistence without compromising their anti-cancer efficacy. Preclinical studies have been completed to obtain valuable data for enhancing the long-term effectiveness of CAR-T therapy in clinical trials and transitioning to clinical applications.

Alzheimer’s disease is the leading cause of dementia worldwide. The neuroprotective impact of essential oil from Apium graveolens L. leaves collected in Türkiye was investigated. The celery leaves oil was extracted by hydrodistillation, and its chemical constituents were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS), followed by anti-beta amyloid cytotoxicity, anticholinesterase, anti-inflammatory, and antioxidant potential. The main essential oil constituents were then tested for their ability to inhibit AChE and BuChE using molecular docking studies. From the essential oil yield (0.1% (w/w)), fourteen components were identified, with l-limonene accounting for the majority (35.4%), followed by cis-ocimene (21.47 %), umbellulone (10.98 %), and enzenemethanol, α-ethyl (10.75%). The oil exhibited significant neuroprotection against Aβ1-42 at a concentration of 1:2x104 dilution from the stock solution (0.1 µl/mL) on SH-SY5Y cells. This concentration increased the viability of cells from 67% to 85.84% against 15 μM Aβ1-42 toxicity. The oil exhibited AChE and BuChE inhibitory potential with (IC50: 22 and 43 µg/mL, respectively). The oil has shown significant antioxidant ability and inhibited COX-1 and COX-2. In all instances, the docking scores for AChE are notably higher than those for BuChE across all tested compounds. Among the investigated test compounds, 1-Limonene exhibits the highest docking scores. In conclusion, the neuroprotective effects of oil highlight its potential for creating novel drugs for AD.