**5.1. Drug design**

16 Apoptosis and Medicine

the ER stress, and then activate JNK pathway, afterwards, JNK activation can stimulate Bax activation; Moreover, calcuim can regulate the cysteine protease calpain, It's well known that calpain participate in the cell proliferation, cell cycle, and apoptosis. Calpain can cleave the N terminal of Bax and generate a proapoptotic fragment, and in the same time, the cells will enter the apoptosis. In a brief, calcium can trigger Bcl-2 independent cytochrome c release, and through regulating the activity of the calpain, calcium iron can play its roles in modulating the apoptosis. [47]. Beside involving in the apoptosis, Cacium iron can take part

As the apoptogenic factor, the permeabilization of lysosomal membrane can induce apoptosis by both caspase-dependent and caspase-independent pathway [48]; Tackled with the unfolded proteins is the one of the important ER functions, cell can regulate the unfolded proteins in ER according to metabolically needed, while if numerous unfolded proteins stimulate the ER and make the ER overload stress, the cells which have lots of unfolded proteins will apoptosis[49]; Differing from the ER stress, chaperons will protect this cell death. For example, the HSP72 protein can hamper the apoptosis through down regulating the unfolded protein signal response sensor IRE1alpha. Some neurodegeneration diseases usually accompany with unfolded protein accelerated and ER stress. So it is meaningful to research the relationship between the ER stress and neurodegenration diseases, and by this way, we will well known the function of apoptosis in the some

The intrinsic components, which can trigger apoptosis pathway, can connect with each other by the vivo organelles. By this way, lots of materials in the cells will consisted in the network of apoptosis to feedback the vitro stimulus, This type cell death will mostly help for

During the last decade, exceptional for the basic research, the apoptosis have attracted many attentions due to its potential application in therapying the various human diseases. In order to maintain the function of whole organism, millions of cells will die and proliferate every day, cell death like apoptosis is the essential for the regulation of organism growth and maintenance the tissue homeostasis. If the cell death and proliferation go to imbalance, many diseases will happen. Such as: some acute pathologies (stroke, heart attack, liver failure); cancer; neurodegenerative syndromes; diabetes and so on. Due to its no lethal effect to the body, Apoptosis play a fundamental role in organism development and tissue homeostasis, while if apoptosis was not under controlled, a variety of diseases will occur.

Some neurodegenerative diseases (Alzheimer's, Parkinson's and Huntington's diseases) usually have the phenomena of the ER dyshomeostasis, mitochondrial dysfunction, and unfolded protein accelerated. In these diseases, some neural cells occur to apoptosis and

in many other signal pathways by controlling the iron channel's open or close.

*4.2.4. Endoplasmic reticulum (ER) stress* 

neurodegeration diseases.

**5. Apoptosis and diseases** 

the body health.

Apoptosis is the normal cell death in order to maintain the balance of homeostasis. Unlikely the necrosis can induce inflammation. apoptosis can give little side effects. So as the therapy targets, apoptosis will be the reasonable way to cure some diseases. such as obesity [50], cancer, neuron-degeneration diseases and so on. Due to the genetic changes often existed in the human tumor cells and apoptosis have the little side effect in curing some diseases, ,it is not surprised that the antitumor drug have direct or indirect to target the apoptosis pathway molecular. The identification of the apoptosis signal pathways, and together with the increased knowledge about the apoptosis mechanisms, have given the great lots of evidences for the discovery of new drugs which can target to the apoptosis.

Above all, from the life beginning and during the whole life, apoptosis always existed to make our life healthy. Apoptosis can not release the intracellular content in the end, this cell process will not lead to inflammation, and therefore, apoptosis is the injury-limiting mode of cell disposal. Above all, it is necessary and meaningful to research the apoptosis mechanism, it will give the deep inside to guild the clinical treatment and drug design. Beside, in the nutrition research area, there are some native compounds which can be from the fruits, vegetables and some marine products can help for healthy through inducing or inhibiting apoptosis signal pathway, so knowing the mechanism of apoptosis deeply not only good for guiding people to use proper drug or balance dietary in daily life, but also far reaching impacts in design some new drugs.
