Linagliptin Case Study

Similarly, an increase in the levels of lipid peroxidation was observed in Aβ-induced rat hippocampal cells, confirming previous reports [17]. Enzymatic antioxidants such as SOD, catalase, and GPX act as the cellular antioxidant defense mechanism against free radicals. Since NADPH is required for the regeneration of catalase from its inactive form, catalase activity might be decreased in Aβ induced toxicity due to reduced NADPH levels. In this study, we have reported that Honokiol treatment significantly increased the enzymatic antioxidant activities in APP-CHO cells. In addition, non-enzymatic antioxidants like GSH also exhibited beneficial neuroprotective effects against oxidative stress. GSH is an endogenous nonenzymatic antioxidant that prevents damage to cellular components caused by ROS such as free radicals and peroxides. GSH is oxidized to glutathione disulfide (GSSG) by ROS, thereby causing a reduction in the level of GSH. GR reduces GSSG to GSH via NADPH, which in turn is released by glucose-6-phosphate dehydrogenase [18]. Honokiol treatment upregulated the activity of these antioxidants in APP-CHO cells. In addition to oxidative stress, a strong association between insulin resistance and the development of AD has been demonstrated. Several studies have reported that insulin resistance (IR), an underlying characteristic of type 2 diabetes, is an important risk factor for AD

Then there is the theory that common diseases or STD's trigger MS and this initiates the migration of white blood cells to enter the brain. Once in the brain these white blood cells activate certain parts of the immune system and thus the immune system begins to attack the myelin that surrounds the nerve. (1) There is another theory that the scarring of the myelin of the nerve is caused by oxidation injury. (3) Oxidation injury is seemingly caused by unstable molecules named free radicals. These free radicals supposedly take electrons from healthy molecules they find in the myelin. These free radicals are also said to occur when the body has been exposed to toxic chemicals. (5) Free radicals are described as punching holes in the cellular walls of our bodies. There is another theory that researchers of MS present. The

Multiple sclerosis (MS) is a potentially disabling disease of the brain and spinal cord, particularly the central nervous system (CNS). In MS the immune system attacks the myelin, which is the protective sheath that covers the nerve fibers and causes communication between your brain and the rest of your body. Eventually, the disease can cause the nerves to deteriorate or even lead to permanent damage. They deteriorate in variable degrees and produce significant disability within 20-25 years in more than 30% of patients, (Luzzio, 2016). The majority of people diagnosed with MS are adults between the ages of 20 and 45; twice as many women are affected compared to men. However, MS can present itself in childhood or late middle age, but is uncommon. According to Goldenberg (2012), there is no known cause for this debilitating disease, but it appears to involve a combination of genetic susceptibility and a nongenetic trigger, such as a virus, metabolism, or environmental factors

Apoliproteins are important players in cholesterol homeostasis. ApoA-I acting as a major HDL component is involved in both HDL biosynthesis and transport. In diseases of the CNS where BBB is compromised, such as MS a healthy cholesterol homeostasis becomes extremely important for neuronal status and regeneration. In as much as S1P receptor agonist fingolimod, Apo-I’s function is not completely understood in this disorder. However all implications are in favor of positive neuroprotective effect of this lipoprotein on the CNS.

The exact cause of MS is unknown. However, its pathogenesis is associated with irregular immune responses against CNS antigens, interference of the blood-brain barrier (BBB) and trans endothelial migration of activated leukocytes, as well as chemokines and cytokines, from peripheral circulation to the CNS. In active disease, there appears to be ongoing inflammatory as well as neurodegenerative processes within the CNS atmosphere. The triggering event for the first attack of MS remains projected. It is assumed that genetic and environmental factors are involved in the progress of MS. (Borazanci, 2009, p. 2)

Mitochondrial dysfunction and oxidative stress have been consistently observed in brains of PD patients. There is increasing pharmacological and genetic evidence sustain a link between PD and mitochondrial respiratory chain dysfunction, particular a deficit in mitochondrial complex I (Franco-Iborra et al., 2015). Accidental exposure to 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP), an mitochondrial complex I inhibitor, has been known to result in acute and irreversible syndrome that was almost indistinguishable from PD (Calne and Langston, 1983; Langston and Ballard, 1983). Later on, mitochondrial complex I inhibition has been identified in the brains of sporadic PD patients (Schapira et al., 1990). In addition, chronic systemic inhibition of mitochondrial complex I by pesticide rotenone has been found to link to sporadic PD (Betarbet et al., 2000). Interestingly, mitochondrial complex I deficiency has been found not only in the postmortem substantia nigra but also in cerebral cortex (Schapira et al., 1990), which is consistent to the cortical glucose hypometabolism observed in PD patients. Indeed, the pathology of PD has been found to involve several brain regions other than the SNc and many neurotransmitters other than dopamine (Lang and Obeso, 2004a, b). PD models using MPTP and rotenone have now been used extensively in PD research (Beal,

Multiple sclerosis (MS) is a neurological disease that affects roughly 400,000 people in the United States (Hunter, 2016) but isn’t very well understood on a cellular level quite yet. There is somewhat of a stigma surrounding the disease as well, as if it is a ticket to life in a wheelchair or an early grave. On the contrary, symptoms and progression vary greatly among individuals and even at different stages for each patient. This paper aims to provide a brief overview of MS, what about it is currently understood, and methods of treatment.

C57BL/6 mice were fed with cuprizone (0.2% w/w) for 12 weeks to induce chronic demyelination and oligodendrocyte degeneration, after which cuprizone was withdrawn to allow recovery. Quetiapine (10 mg/kg/day) or vehicle (water) was administrated orally to mice for 0, 2, 3, or 4 weeks after cuprizone withdrawal. Locomotor activity and Y-maze tests were used to evaluate behavioral changes in the mice. Immunohistochemical staining was

Generally, two surface molecules including complement receptor type 3 (CR3) and galactose-specific lectin MAC-2 are involved in Wallerian degeneration process and consequently the peripheral nerve regeneration. However, injury to CNS is not followed by extensive regeneration. It is limited by the inhibitory influences of the glial and extracellular environment. The environment within the CNS, especially following trauma, counteracts the repair of myelin and neurons. Growth factors are not expressed or re-expressed; for instance, the extracellular matrix is free of laminin, so glial scars rapidly form and produce factors that inhibit re-myelination and axon repair. The axons themselves also lose the potential for growth with age due to a decrease in the expression of

(MS) is a chronic inflammatory, demyelinating, autoimmune neurodegenerative disease characterized by the disruption of the blood brain barrier (BBB), perivascular inflammation, axonal and oligodendrocyte injury, and breakdown of the myelin sheath present in the central nervous system (CNS). The Loss of myelin leads to progressive axonal damage and eventually neuronal death, resulting in neurodegeneration and functional disability in different regions in the brain and the spinal cord. According to the domain which is compromised, it could cause various symptoms such as motor dysfunction, sensory distortion, visual impairment, dyscoordination, fatigue, bladder dysfunction, cognitive impairment and depression (Goldenberg et al.,2012), and is characterized With remissions and recurring exacerbations of the disease.

More than 400,000 of people are diagnosed with Multiple Sclerosis (MS) in America and approximately 2.3million cases in the world (Multiple Sclerosis International Federation, 2013). Multiple Sclerosis is one of the most common neurological diseases of the central nervous system (CNS) (Wei, 2014). The myelin sheath that wraps around the nerve fibers is being attacked by our body immune system, which affects the body’s actions and responses as cell-to-cell communication to and from the brain is delayed (Mendes, 2016). The disease commonly affects people between the age of 20 to 50, and women are more likely than men to develop the disease (Multiple Sclerosis International Federation, 2013).

Multiple System Atrophy (MSA) is an adult onset progressive neurodegenerative disease, characterized by various degrees of Parkinsonism, cerebellar ataxia, and failure of the autonomic nervous system. MSA is classified as a α-synucleinopathy, a subset of neurodegenerative diseases characterized by the accumulation of misfolded α-synuclein (α-Syn) in the CNS (Fellner et al., 2011; MartÌ et al., 2003). In MSA, α-syn aggregates appear primarily as glial cytoplasmic inclusions (GCIs) in oligodendrocytes (Wakabayashi et al., 1998). The accumulation of α-syn aggregates is associated with glial pathology and neuroinflammation in MSA and other α-synucleinopathies such as, Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) (Fellner et al., 2011). Microglia activation has also been implicated in α-synucleinopathies as well as other neurodegenerative disorders including Alzheimer’s disease (AD) and Multiple Sclerosis (MS) (Fellner et al. 2011; Minagar et al., 2002).

Multiple Sclerosis (MS) is a non-preventable inflammatory neurodegenerative demyelinating disease. The pathogenesis of MS is a debatable topic and still needs to be better understood. (1,3) .

Specifically, nitric oxide has been identified contributing to neuroaxonal degeneration.1, 9, 10 Studies in the spinal cord and lateral geniculate nucleus in MS patients have shown a greater loss of small axons in comparison to larger ones.10 This is because smaller axons are more susceptible to inflammatory mediators like nitric

The presence and activities of these cells in patients with early cases and mature stages of MS are examined and carefully analyzed. Results demonstrated a considerable decrease in the NogoA+ and Olig2+ cells for individuals with chronic MS, but those in the early stages of MS showed a different result. Moreover, during the demyelination phase, repeated stimulation of SCD in the experimental rats stemmed to a transitory loss of NogoA+ but did not have a similar effect on the Olig2+ cells. This was followed by the complete repopulation and remyelination of the oligodendroglial cells, notwithstanding the four preceding periods of demyelination. These results indicate successful remyelination in subpial cortical lesions among the rats even after repeated SCD, an indication only apparent to early MS but not to chronic cases. Furthermore, the data obtained demonstrated that the four cycles of continuous demyelination and remyelination process did not effectively sustain an independent remyelination that has been observed in chronic MS lesions. The results of the