Current Protein and Peptide Science - Volume 22, Issue 6, 2021

The transdermal therapeutic system plays an important role in the treatment of neuropathic pain. Transdermal drug delivery is considered an ideal therapeutic approach for the management of chronic neurological disorders in the elderly population. It is a simple to use, non-invasive and painless drug delivery system, which provides sustained therapeutic plasma levels of drug for an extended period. Moreover, it bypasses the first-pass metabolism of the active agent, improves bioavailability and reduces undesired adverse effects, which in turn improves patient compliance. Several transdermal delivery systems are currently under investigation for the treatment of Parkinson’s syndrome, Alzheimer’s disorders, and Neurological pain. Drug delivery via the transdermal route is proposed as an alternative remedy to overcome the drawbacks associated with the conventional dosage forms for chronic neurological disorders. The management of Alzheimer’s disease via transdermal drug administration exhibits the greatest therapeutic improvements in the treatment of cognition and global functioning among neuropathic patients. Technological breakthroughs in transdermal drug administration such as the microreservior system, microneedles, metered-dose transdermal spray (MDTS), needle-free injections, and ultrasound-based transdermal therapeutic systems have been successfully used to treat neurological disorders. For example, microneedle (MN) is a highly efficient and versatile device due to its distinctive properties. Ultrasounds have been very popular for the delivery of bioactive agents across the skin barrier. This review focuses on the recent advances of various technologies employed in the transdermal therapeutic systems and their applications on neurological disorders for achieving therapeutic outcomes on patients.

The fusion of secretory vesicles with the plasma membrane depends on the assembly of v-SNAREs (VAMP2/synaptobrevin2) and t-SNAREs (SNAP25/syntaxin1) into the SNARE complex. Vesicles go through several upstream steps, referred to as docking and priming, to gain fusion competence. The vesicular protein synaptotagmin-1 (Syt-1) is the principal Ca²⁺ sensor for fusion in several central nervous system neurons and neuroendocrine cells and part of the docking complex for secretory granules. Syt-1 binds to the acceptor complex such as synaxin1, SNAP-25 on the plasma membrane to facilitate secretory vesicle docking, and upon Ca²⁺-influx, it promotes vesicle fusion. This review assesses the role of the Syt-1 protein involved in the secretory vesicle docking, priming, and fusion.

The current meta-analysis of the cohort review was designed to elucidate the progress made in neuroproteomics of the synaptosome. The association of the comprehensive synaptic proteome and its link to physiological or pathological setting is rapidly mounting. Chemical synapses in the brain are focal hot spots for interneuronal signalling, signal transduction, and its plasticity. Structurally, synapses comprise axon termini or the presynapse (vesicles filled with neurotransmitters that function as molecular signals), synaptic clefts (extracellular matrix and adhesion molecules), and Postsynaptic Density or PSD (with receptors for neurotransmitters that rely upon the chemical signalling). The pre- and post-synaptic clefts are responsible for mediating and regulating neurotransmitter release, their receptor binding, and perception rely on chemical signals. Moreover, short- and long-term structural and functional alterations that are necessary for the optimal higherorder brain functions are also mainly dependent on the protein dynamics at the synapses. Not surprisingly, disruptions in synaptic physiology are considered as the major pathogenic mechanisms underlying the progression of several neurodegenerative disorders, including Alzheimer's disease. This review briefly discusses the subcellular fractionation protocols and the related biochemical approaches for the isolation of synaptic compartments. Besides, it discusses the progress made in understanding the pathological alterations in the synaptic proteome in neurodegenerative disorders, particularly focussing on Alzheimer's disease dementia.

Over the past few decades, immunotherapy has emerged as a promising therapeutic approach to treat some types of cancer. Moreover, antibody-based cancer therapies can trigger apoptosis and cell growth inhibition to induce immune cell destruction of target cells through antibody-dependent cellular cytotoxicity (ADCC). Nevertheless, immunotherapeutic efficiency is often restricted due to deficient delivery or low accumulation of therapeutic molecules at the tumor site. The development of pegylated liposomes with monoclonal antibodies conjugated to their surfaces (immunoliposomes) and triggered with ultrasound can effectively improve drug accessibility by enhancing cell membrane permeability and drug release. This review summarizes existing traditional cancer treatments and their limitations, emphasizing the recent advancements in ultrasound-triggered immunotherapy.