الفهرس | Only 14 pages are availabe for public view |
Abstract Parkinson’s disease is a widespread neurodegenerative disorder, affecting up to 2% of individuals over 65 and 10% of people over 80 years old. Besides motor dysfunction, cognitive deficits have also been reported in PD patients. Clinical studies revealed mild cognitive deficits in " ~ "30%-40% of newly diagnosed patients, and dementia in nearly 60%-80% of patients in the advanced stage of the illness, which has a negative impact on their life expectancy, and everyday functioning, and greatly impairs their quality of life. The mechanisms underlying cognitive abnormalities in PD remain unclear and are usually undiagnosed and, consequently, untreated. Numerous researchers believe that not only neurochemical alterations in dopaminergic, cholinergic, and other systems but also neuropathological contributions of limbic and cortical Lewy bodies and neurites, amyloid deposition, NFTs, and even cerebrovascular disease, mitochondrial dysfunction, oxidative stress, inflammation, autophagy dysfunction, and neurotrophic factors have frequently given rise to cognitive deficits in PD. Current pharmacotherapy is limited to symptom relief, particularly in the field of motor symptoms. However, these drugs do not stop the progression of the disease and have incapacitating side effects when used for an extended period of time. The lack of a meaningful treatment that can be used after the disease is currently the main barrier to progress in the fight against Parkinsonism. As a result, new PD strategies are required to prevent or slow the progression of motor and cognitive symptoms. Type 2 DM shares pathophysiological mechanisms with PD and neurodegenerative dementias, such as central and peripheral insulin resistance, which leads to altered autophagy, cell proliferation, and increased inflammation. As a result, evaluating the potential repurposing of existing anti-diabetic drugs in the prevention of ROT-induced cognitive deficits in PD is of great interest. Sitagliptin, a drug that belongs to a group of medications that inhibits the DPP-4 enzyme, PIO, a TZD derivative drug, which activates PPAR-γ receptors both are useful glucose-lowering agents for patients with type 2 DM. These drugs have been explored by various researchers to treat cognitive abnormalities linked to neurodegenerative disorders due to their neuroprotective effects, including antioxidant, anti-inflammatory, antiapoptotic, autophagy-modulating, and neurotrophicsupporting properties. |