Role of Apoptosis in disease

Dipartimento di Scienze Biomediche, Universita' "G. d'Annunzio" Chieti-Pescara, Italy.
Aging (Impact Factor: 6.43). 05/2012; 4(5):330-49.
Source: PubMed


Since the initial description of apoptosis, a number of different forms of cell death have been described. In this review we will focus on classic caspase-dependent apoptosis and its variations that contribute to diseases. Over fifty years of research have clarified molecular mechanisms involved in apoptotic signaling as well and shown that alterations of these pathways lead to human diseases. Indeed both reduced and increased apoptosis can result in pathology. More recently these findings have led to the development of therapeutic approaches based on regulation of apoptosis, some of which are in clinical trials or have entered medical practice.

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    • "An extensive screening of 150 brain-expressed genes encoding ion channels, transporters, exchangers, and their associated regulatory subunits revealed that the Kv6.4 gene was potentially linked to migraine: the L360P missense mutation in the Kv6.4 gene was found only in migraine patients (compared with nonmigraine control patients;Lafrenière and Rouleau, 2012). Apoptosis is crucial to the normal development of several tissues and is also involved in various neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease (Favaloro et al., 2012). An up-regulated K + current through Kv2.1 channels resulting in a disturbed K + homeostasis is a key factor in the early apoptotic cascade (Pal et al., 2003). "
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    ABSTRACT: Members of the electrically silent voltage-gated K(+) (Kv) subfamilies (Kv5, Kv6, Kv8, and Kv9, collectively identified as electrically silent voltage-gated K(+) channel [KvS] subunits) do not form functional homotetrameric channels but assemble with Kv2 subunits into heterotetrameric Kv2/KvS channels with unique biophysical properties. Unlike the ubiquitously expressed Kv2 subunits, KvS subunits show a more restricted expression. This raises the possibility that Kv2/KvS heterotetramers have tissue-specific functions, making them potential targets for the development of novel therapeutic strategies. Here, I provide an overview of the expression of KvS subunits in different tissues and discuss their proposed role in various physiological and pathophysiological processes. This overview demonstrates the importance of KvS subunits and Kv2/KvS heterotetramers in vivo and the importance of considering KvS subunits and Kv2/KvS heterotetramers in the development of novel treatments.
    No preview · Article · Jan 2016 · The Journal of General Physiology
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    • "Aberrant activation of caspases has been implicated in a number of conditions, including autoimmunity, transplant rejection and heart failure (Ocker and Höpfner, 2012). Manipulating caspase signaling has a therapeutic benefit on diverse diseases, such as cardiovascular, autoimmune and infectious disease (Favaloro et al., 2012). "

    Full-text · Dataset · Nov 2015
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    • "The control or any disorder in it has the effective role in malignant deformation process, cancer progress and metastases (Bold et al., 1997; Kamesaki et al., 1998). Apoptosis is done through two different pathways including the death-receptor pathway and mitochondrial pathway (Favaloro al., 2012). The B-cell lymphoma 2 (Bcl-2) family represents apoptosis regulating proteins integrating diverse intra-and extracellularly generated survival and death signals. "
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    ABSTRACT: Gastric cancer accounts for about 8% of the total cancer cases and 10% of total cancer deaths worldwide. It is the second lethal cancer after esophageal cancer and is considered the fourth most common cancer in north and northwest Iran. The bcl2 family has a key role in the regulation of apoptosis and change in its expression can contribute to cancer. This study initially scheduled to determine the expression of bcl2 gene in tissue samples of adenocarcinoma cancer patients. A total of 10 samples of gastric adenocarcinoma and 10 of normal tissues from Sari hospital were selected and after DNA extraction from tissues, bcl2 gene expression assayed by real-time PCR. Our results demonstrated higher expression of the bcl2 gene in control compared with cancer and marginal cancer tissues. On one hand BCL2 plays an important role as an oncogene to inhibit apoptosis; on the other hand, it can initiate cell cycle arrest at G0 stage. Our observed association between its expression and patient survival is quite conflicting and may be tissue-specific. The data suggest expression both tumoural and non-tumoral(marginal) groups have lowered expression than controls (P>0.05). Due to the low number of samples we could not examine the relationship with clinicopathological features. However, bcl-2 expression may be important for prognostic outcome or a useful target for therapeutic intervention.
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