**6.22 Prion disease**

It is also known as "Transmissible Spongiform Encephalopathies" (TSEs), a rare group of degenerative brain disorders describe by minute holes that cause the brain a "spongy" appearance.

#### **6.23 Sandhoff disease**

It is caused due to the deficiency of the enzyme beta-hexosaminidase, which is the result of the accumulation of certain fats in the brain and other organs of the body. It is a rare, genetic disorder resulting in a progressive decline of the central nervous system.

#### **6.24 Shy-Drager syndrome**

It is a neurological disorder also known as multiple system atrophy with orthostatic hypotension causes dizziness and fainting. Doctors classify the disorder into 3 types


It is a progressive disorder of the central and autonomic nervous systems were problems with urinary incontinence, weakness double vision, constipation and decreased sweating.

#### **6.25 Tabes dorsalis**

It is a slow degeneration of the nerve cells and nerve fibres that transmit sensory information to the brain. These nerves are in the dorsal columns of the spinal cord and carry out a signal which helps to maintain an individual's sense of position.

#### **7. Recent progress in preventing neurodegenerative diseases**

It is known that neurological disorder which includes Alzheimer's disease (AD), Multiple sclerosis (MS), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic lateral sclerosis (ALS) that noticeable in millions of people throughout the world every year. The common feature of these disorders is neuronal loss and the outcome is locomotor difficulties, cognitive defects, and chronic deterioration in memory.

Hence the researchers are following a collaborative approach to preserving the function and groups of neural tissues before the damage. This neuroprotective approach concentrates on the improvement in strategies that prevent most neuronal death.

#### **8. Prevention of self-directed neurodegeneration**

To maintain and restore physiological homeostasis cell has a variety of self-repair mechanism. Whenever a cell loses the capacity to overcome the damage, intracellular homeostasis falls and stimulates a series of cell death events takes place. Research over a few years and studies have shown that apoptotic cell death is not the only pathway directing the loss in these disorders. Among them, poly (ADP-ribose)

(PAR)-dependent cell death has been started as being responsible for neuronal loss in various neurological disorders, comprising AD, ALS, HD, and PD. Oxidative stress injured DNA, resulting in PAR1 activation due to excessive accumulation of intracellular PARP1 [5]. Parthanatos is the result of numerous cellular processes, consisting release of apoptosis-inducing factor (AIF) from mitochondria, overactivation and macrophage migration inhibitory factor (MIF) and co-translocation of AIF into the nucleus, directing to DNA fragmentation and cell death [6, 7].

Overactivation of PARP1 and PAR accumulation have been noticed in the brains of AD patients [8, 9]. Studies have revealed that neurons are guarded by PARP1 inhibition, which means that PARP1 inhibition may have therapeutic importance for the treatment of AD.

Modern discoveries in the PD model show more direct facts that in pathologic α-synuclein neurodegeneration, parthanatos is the most important cell death pathway. In this PAR is the main mediator, encouraging α-synuclein toxicity and fibril conducting, exacerbating neurotoxicity in a feed-forward loop [10]. Oral administration of PARP1 inhibitor and genetic reduction of PARP1 stopped neurodegeneration and progresses motor capability in both genetic and sporadic models of PD [10, 11]. Moreover, increased PAR levels in the cerebral spinal fluid and brains of patients with PD [10], recommend that PARP1 might be a theragnostic biomarker and a disease-modifying therapeutic goal in PD [12]. Elongated polyglutamine (poly Q ) is responsible for Huntington (htt) protein aggregation along with neuronal inclusions and toxicity in HD [13].

Enhanced PAR levels and dysregulation of PARP1 activation contribute to the pathogenesis of several neurodegenerative diseases by promoting parthanatos and protein aggregation. Therefore, a neuroprotective course of action intended to reduce PARP1 activation may have therapeutic potential in those disorders. Several well-described PARP inhibitors are in experimental use and yet to be tested for use in neurodegenerative disorders [14]. Thus these can be regarded as a neuroprotective treatment for neurological disorders.
