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Medicinal Chemistry


ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Apoptosis Signaling Pathways in Lung Diseases

Author(s): K. Kuwano, M. Yoshimi, T. Maeyama, N. Hamada, M. Yamada and Y. Nakanishi

Volume 1, Issue 1, 2005

Page: [49 - 56] Pages: 8

DOI: 10.2174/1573406053402497


Evidence that apoptosis plays an important role in the pathophysiology of lung diseases has been accumulated. Apoptosis signaling is classically composed of two principle pathways. One is a direct pathway from death receptor ligation to caspase cascade activation and cell death. Death receptor ligation triggers recruitment of the precursor form of caspase-8 to a death-inducing complex, through the adaptor protein FADD, which leads to caspase-8 activation. The other pathway triggered by stimuli such as drugs, radiation, infectious agents and reactive oxygen species is initiated in mitochondria. After cytochrome c is released into the cytosol from the mitochondria, it binds to Apaf1 and ATP, which then activate caspase-9. Recently, endoplasmic reticulum has also been shown to be the organelle to execute apoptosis. Further understanding of molecular mechanisms of apoptosis and its regulation by novel drugs may lead to the development of effective strategies against lung diseases. We overview the signaling pathways of apoptosis and discuss the involvement of apoptosis in the pathophysiology of various lung diseases.

Keywords: apoptosis, death receptor, mitochondria, acute lung injury, pulmonary fibrosis, bronchial asthma, pulmonary emphysema

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