WITHDRAWN: Revisiting the cholinergic hypothesis in Alzheimer's disease: Emerging evidence from translational and...

Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...

Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...

Neurotransmitters are integral to the brain's communication system, enabling neurons to transmit signals across synapses. This chemical exchange underpins various cognitive functions, including memory processes. The role of neurotransmitters in memory is multifaceted, influencing the encoding, consolidation, and retrieval of memories through their action on different neural circuits.
 Glutamate and Synaptic Plasticity
Glutamate, the brain's main excitatory neurotransmitter, is...

Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...

Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function.

Cholinergic neurotransmission involves the synthesis and the release of acetylcholine (ACh) in order to transmit nerve impulses across the synapse. The process begins with the synthesis of acetyl CoA, a precursor for ACh, from ATP, acetate, and coenzyme A in the mitochondria. Choline, another vital precursor, is transported inside the neuron through choline transporters, including high-affinity choline transporter CHT1, low-affinity choline transporter CTL1, and lower-affinity choline...