**2. Mechanism of action of lipid peroxidation (LPO)**

The process of LPO on membrane influences discrete functions from the increased rigidity of membrane, reduced action of membrane-confined enzymes, impairment of membrane receptors and modified permeability of the cell membrane. Similar to phospholipid impairment, radicals can also directly attack lipidprotein and membrane proteins mediate as well as protein–protein interconnection, subsequently affect the membrane integrity [28]. LPO products persuade such a loss of membrane integrity that ultimately leads to unadorned cytotoxicity, and could result in unrestrained cellular growth or even apoptosis. Rationally, the perturbation of the above-mentioned functions ensued by polyunsaturated fatty acids, along with the resultant metabolites and protein insults modifies the neuronal homeostasis, and leads to the multi-organ organ dysfunction [29–31].

## **3. Lipid peroxidation (LPO) products as biomarkers in neurodegenerative disorders**

LPO products are significantly associated to the development of Alzheimer's diseases (AD); and hence, they are studied as potential disease signaling biomarkers in neurodegenerative disorders. LPO products such as MDA, IsoPs, TBARS, and fluorescent lipofuscin-like pigments (LPF) extensively studied and found in different human samples (plasma, serum and urine) of the patients suffering from neurodegenerative disorders. (Summarized in **Table 1**).

Histopathological studies revealed a co-localization of lipid peroxidation products and β-amyloidplaques in the brain of the AD. Also, the studiy evident for the presence of fatty acids in AD brain lesions produced a neurotoxic effect in cell culture increasing oxidative stress [41]. Since the brain contains high lipid content and high oxygen consumption, lipid peroxidation seems to play fundamental role in AD early detection. Similarly, IsoPsand its isomers produced via diverse actions that, are encountered as marginal oxidation products of the arachidonic acid [42]. Whereas, neuroPsenriched in the neuronal tissue and vital component


#### **Table 1.**

*Signaling mechanism of lipid peroxidation in biological samples of patients.*

of the nervous tissues, awfully susceptible to oxidation [43]. Thus, the quantitative estimation of neuroPsaffords a significantsource of oxidative neuronal impairmentcorresponding to IsoPs [44].

Malondialdehyde (MDA) a signaling molecule of LPO has ability to interact with micro-macromolecules such as nucleic acid bases, developingdivergent adducts, and can also react with proteins in a synergistic and covalent manner, subsequently, leads to the stimulation of strong immune responses and exhibits pro-fibrogenic and pro-inflammatory properties/mediators such as interleukins, cytokines etc. Furthermore, accumulation of MDA modifies membrane integrity by inducing increased intra and extracellular permeability and damage the fluidity of membrane lipid bilayer. Being a most mutagenic, MDA is capable of reacting with deoxyadenosine in DNA and deoxyguanosine, thus generating mutagenic DNA adducts [21, 31].

As the consequence of peroxidation of PUFAs (linoleic and arachidonic acid), Hudroxy-2-nonrenal (HNE) are formed, since they are the most abundant in fatty acids. The HNE, specifically, bind to amino acids mainly: cysteine, histidine and lysine proteinaceous residue addition by either the amino and thiol groups. The conjugates of protein residue and HNE, leads to the impairment of the normal protein function as well as structure, and also HNE exhibits reactivity with vital nucleic acids, lipids, signaling biomolecules and vitamins. Documented reports, suggests that, the HNE accumulates in extremely low concentration (10 μM), in response to oxidative stress and induces cytotoxicity and selective suppression of inducible and basal NF-kB factors. Therefore, increased levels of HNE results in Ca2+ homeostasisimbalance, disruption of glutamate transport, membrane impairment, microtubule function, and cellular death via the activation of caspase pathways [28, 45].

#### *Lipid Peroxidation: A Signaling Mechanism in Diagnosis of Diseases DOI: http://dx.doi.org/10.5772/intechopen.99706*

Threonine metabolite product, acrolein generated by the bio activation of phagocytes and cyclophosphamide. Wherein, acrolein targets histidyl, lysyl and cysteinyl residue of protein side chain as well as reactswith nucleophilic sites in DNA, that results in DNA and protein adducts and, thus, initiates cytotoxicity specifically related to its ability to reduce glutathione [46]. Docosahexaenoic acid (DHA) enriched in neurons, and is a vital compound of the nervous tissue. It is a vital compound of the nervous tissue and enriched in neurons and extremelysusceptible to oxidation. DHA on oxidative stress, leads to the production of Neuroprostanes (F4-isoprostanes). In a biological aspect, neuroPsillustrates anti-inflammatory properties by inhibiting proteasome concentrated in the neurons membrane [45]. Nevertheless, the central nervous system (CNS) is one of the major targets of the LPO and proneto chain reactions induced by ROS, which eventually result in LPO products [47]. The role of LPO quantification in the pathogenesis of NDs is significant and extremely importance for the early detection of neurodegenerative disorders [45].

The most frequently exploited LPO products such as lysine residues and unsaturated aldehydes, including HNE and aracolein [48]. Several research studies have been probing the LPO products and disease state interrelation, and its application as possible biomarkers in order to assess prognosis and establish early detection of the disease [49]. Among the above-mentioned potential biomarkers, IsoPssignifies the most reliable and robust outcomes. Moreover, the IsoPs accurately process and assessed the oxidant stress *in vivo*via quantification of plasma and urinary sample. Also, *in situ* phospholipids composed of IsoPs that locates the free radical production and release from the cellular membrane via phospholipases in the plasma. IsoPs detected and quantified in a plethora of biological fluids including plasma cerebrospinal fluid, exhaled breath condensate, urine and bile [50]. On the other hand, neuroPs are a fundamental component of the nervous tissue, enriched in the neuronal tissue and extremely susceptible to oxidation [51]. Thus, the quantification of neuroPs provides a signaling biomarker of oxidative neuronal damage compare to IsoPs quantification. In addition, the quantity of neuroPs produced

from DHA surpass that of IsoPs from arachidonic acid by 3.4 folds. NeuroPsare elevated in the cerebrospinal fluid and brain tissue in ND, such as Parkinson and Alzheimer's disease. Hence, quantification of neuroPs levels isa vital tool in evaluating brain oxidative impairment [52]. Whereas, crosslinking is a major factor in the development of pathology due to the promotion of intramolecular or intermolecular DNA and protein cross-linking, which results in intense change in the biochemical properties of various biomolecules (**Figure 1**). This articulated process is assumed to be a channel of interrelation chain reactions with covalent nucleophilic compounds. Also, the translated and interconnected experimental indicators with precise altered proteins in the CNS exhibited those definite cellular amendments are in concomitant with pathophysiology of Neurodegenerative diseases. Thus, the revival of scientific data affords a comprehensive knowledge in the advancement and employment of LPO products as potential biomarkers in the early diagnosis of the disease, alteredbiological processes, revealing potential active sites to target disease progression (**Figure 2**).
