**8. Challenges of the future**

The aim of the future will be to develop an accurate map of omic data of the ageing process. This is associated with the problem of collection of the samples for multiomics data from a human across lifespan. Second, the factors that can be a source of a noise in the omic data should be identified, including information on the ethnicity, personal immunological history or parameters of lifestyle (dietary habits, physical activity and microbiological status). Comprehensive of integrative interactomics of (epi)gene-protein-pathways axis would demand more advanced and consolidated computational, mathematical and bioinformatic tools. These methods should integrate the data obtained with a use of various methodological approaches and engines, from different biological range and integrate the statistical power for all of them. Further aspects, which require to be consolidated or demand additional computational approaches, are related to the source material (tissues and cells) used for omics analyses. These and other criteria must be met to be able to pinpoint the cause and prevent a decline in cognitive skills, so important in everyone's life.

### **9. Summary**

Neurodegeneration in AD or PA is a multiparametrical process. Thus, there is a need of not only for an establishment of the most complete genetic background but also to pinpoint the functional implications of this knowledge. Despite strong efforts of the recent research, based mostly on modern technologies, including GWAS and WES, it is still a largely unknown domain. It is very likely that expanding the interactomes PS1 and PS2 will help to emerge the complex biological processes accompanying processing of many substrates of presenilins. The broad spectrum of γ-secretase substrates and interacting proteins has invoked the analogy to γ-secretase 'secretosome' or 'proteasome of the membrane'. The complexity of the interactome of presenilin 1 is implicated in a number of molecular functions, manifested in different cell components and implicated in a variety of biological processes, crucial for Alzheimer's disease and pathological ageing, and is depicted in a schematic presentation of this chapter (**Figure 1**). Additionally, it is important to take into account environmental factors, for example, psychological circumstances might affect gene expression profile via epigenetical mechanisms, and thus presenilins interacting network, with further functional implications. In conclusion, the understanding of existing genetic mechanisms together with presenilin functions leading to brain degeneration in AD or PA is crucial for better understanding of molecular bases of these pathologies and facing them in the future.

Presenilins Interactome in Alzheimer's Disease and Pathological Ageing http://dx.doi.org/10.5772/intechopen.68748 107

**Figure 1.** The interactome of presenilin 1 in Alzheimer's disease and in pathological ageing. Presenilin 1 interactome was generated using Ingenuity Pathway Analysis software (www.ingenuity.com). Presenilin 1 interactome is implicated in a number of molecular functions, cell components and biological processes of presenilin 1, according to GeneCards®: The Human Gene Database. Presenilin 1 interaction network with its functional consequences are crucial both for Alzheimer's disease and for pathological ageing brains.

## **Acknowledgements**

and multi-level nature of the network of genes, proteins, their interactomes and relationships with ageing-related disease processes present in both AD and PA have been reported in several recent review papers [94, 98, 105–107]. This and other reviews underline the importance of the integration of different biological data provided for the process of brain degeneration,

The aim of the future will be to develop an accurate map of omic data of the ageing process. This is associated with the problem of collection of the samples for multiomics data from a human across lifespan. Second, the factors that can be a source of a noise in the omic data should be identified, including information on the ethnicity, personal immunological history or parameters of lifestyle (dietary habits, physical activity and microbiological status). Comprehensive of integrative interactomics of (epi)gene-protein-pathways axis would demand more advanced and consolidated computational, mathematical and bioinformatic tools. These methods should integrate the data obtained with a use of various methodological approaches and engines, from different biological range and integrate the statistical power for all of them. Further aspects, which require to be consolidated or demand additional computational approaches, are related to the source material (tissues and cells) used for omics analyses. These and other criteria must be met to be able to pinpoint the cause and prevent a

Neurodegeneration in AD or PA is a multiparametrical process. Thus, there is a need of not only for an establishment of the most complete genetic background but also to pinpoint the functional implications of this knowledge. Despite strong efforts of the recent research, based mostly on modern technologies, including GWAS and WES, it is still a largely unknown domain. It is very likely that expanding the interactomes PS1 and PS2 will help to emerge the complex biological processes accompanying processing of many substrates of presenilins. The broad spectrum of γ-secretase substrates and interacting proteins has invoked the analogy to γ-secretase 'secretosome' or 'proteasome of the membrane'. The complexity of the interactome of presenilin 1 is implicated in a number of molecular functions, manifested in different cell components and implicated in a variety of biological processes, crucial for Alzheimer's disease and pathological ageing, and is depicted in a schematic presentation of this chapter (**Figure 1**). Additionally, it is important to take into account environmental factors, for example, psychological circumstances might affect gene expression profile via epigenetical mechanisms, and thus presenilins interacting network, with further functional implications. In conclusion, the understanding of existing genetic mechanisms together with presenilin functions leading to brain degeneration in AD or PA is crucial for better understanding of

in both PA and AD, and other neurodegeneration disorders with dementia.

decline in cognitive skills, so important in everyone's life.

molecular bases of these pathologies and facing them in the future.

**8. Challenges of the future**

106 Senescence - Physiology or Pathology

**9. Summary**

This work was supported by the National Science Centre (Poland) grant 'SONATA6' no. G1119-2013/09/D/NZ3/01348 and by Statutory Grant of Mossakowki Medical Research Centre from Ministry of Science and Higher Education.
