**9. Impede of non-cell-autonomous neurodegeneration**

In neuronal support, glial cells play a key role in maintaining homeostasis, neurogenesis and nutrient transportation in healthy brains, [15]. Notably, an emerging research body has shown that dysfunctional non-neuronal cells such as astrocytes and microglia straight supply to neurodegeneration and cell death (Thus called non-cell autonomous neurodegeneration) in several neurodegenerative disorders.

Microglia are the inhabitant macrophages and primary immune cells in the brain. Hence they play a significant role in neuronal disease. In the post-mortem of AD brains, reactive microglia are present and have been shown to encourage synaptic drop and neuroinflammation [16, 17]. In the glial cells many PD-related genes, incorporating α-synuclein, PINK1, and parkin, are expressed. During PD pathogenesis mutated gene products are engaged in microglial dysfunction.

In review, microglia is believed to have both useful and harmful functions in neurodegenerative diseases. Therefore, the introduction of subsequent prevention of neurotoxic microglia signature and DAM (disease-associated microglia) or homeostatic microglia signature could be assuring therapeutic approaches for neuroprotection in neurodegenerative diseases, but the elements allied with heterogenous microglial phenotype will require to be defined in further detail.

The most abundant population of glial cells in the CNS is the astrocytes which carry out a broad range of homeostatic functions. So it is not surprising that the loss of the usual normal astrocyte role is engaged in the pathogenesis of neurodegenerative diseases. According to a 2017 investigation, activated microglia induce the formation of neurotoxic reactive astrocytes by releasing interleukin 1α (IL-1α), tumour necrosis factor α (TNF-α), and C1q [18]. In the post-mortem of the human brain, neurodegenerative diseases like AD, PD, ALS, and HD reactive astrocytes were found [18].

Currently, though, it has been observed that the phenotype variety of astrocytes is noticed in brains with neurodegenerative diseases and widens beyond the A1 and A2 phenotypes [19–24]. Hence further research is required to know more about the molecular mechanisms of reactive astrocytes and their particular role within different neurodegenerative pathologies, specifically how the neurotoxic signals interchange and are shared across multiple neurodegenerative conditions.

## **10. Conclusion**

There is a number of factors which cause neurodegenerative diseases such as neuronal cell death, genetic mutations, protein aggregation, flawed protein recycling, mitochondrial dysfunction, and innate immune responses due to glial cell activation. Hence neuroprotection can be achieved from cell-autonomous neurodegeneration directly by attacking their neighbouring cells. Thus, to prevent or slow neurodegeneration a multifaceted approach attacking both cell-autonomous and non-cellautonomous mechanisms may be required.

To understand neurodegeneration, the molecular mechanism is an important footstep in the development of novel neuroprotective therapies. Due to remarkable efforts, these therapies have developed beyond the lab to the clinical testing stage. Thus, further research in the neurodegenerative pathways and the development and identification of neuroprotective agents are required to build up promising diseasemodifying therapeutic approaches for the management, handling, and treatment of the neurodegenerative diseases.

## **Author details**

Safiya Tazeen\* and Mohammed Ibrahim KBN University, Gulbarga, India

\*Address all correspondence to: tazeenchishti@gmail.com

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
