The interlink between diabetes mellitus and neurodegenerative diseases such as Alzheimer’s
Disease (AD) and Parkinson’s Disease (PD) has been identified by several researchers. Patients
with Type-2 Diabetes Mellitus (T2DM) are found to be affected with cognitive impairments
leading to learning and memory deficit, while patients with Type-1 Diabetes Mellitus (T1DM) showed
less severe levels of these impairments in the brain. This review aimed to discuss the connection between
insulin with the pathophysiology of neurodegenerative diseases (AD and PD) and the current
therapeutic approached mediated through insulin for management of neurodegenerative diseases. An
extensive literature search was conducted using keywords “insulin”; “insulin resistance”; “Alzheimer’s
disease”; “Parkinson’s disease” in public domains of Google scholar, PubMed, and ScienceDirect.
Selected articles were used to construct this review. Studies have shown that impaired insulin
signaling contributes to the accumulation of amyloid-β, neurofibrillary tangles, tau proteins and
α-synuclein in the brain. Whereas, improvement in insulin signaling slows down the progression of
cognitive decline. Various therapeutic approaches for altering the insulin function in the brain have
been researched. Besides intranasal insulin, other therapeutics like PPAR-γ agonists, neurotrophins,
stem cell therapy and insulin-like growth factor-1 are under investigation. Research has shown that insulin
insensitivity in T2DM leads to neurodegeneration through mechanisms involving a variety of extracellular,
membrane receptor, and intracellular signaling pathway disruptions. Some therapeutics,
such as intranasal administration of insulin and neuroactive substances have shown promise but face
problems related to genetic background, accessibility to the brain, and invasiveness of the procedures.
Investigation of Insulin Signaling in Parkinson's Disease Cytoplasmic Hybrid Cells