Histone deacetylases (HADC) are the enzymes that remove acetyl group from lysine residue of histones and non-histone proteins and regulate the process of transcription by binding to transcription factors and regulating fundamental cellular process such as cellular proliferation, differentiation and development. In neurodegenerative diseases, the histone acetylation homeostasis is greatly impaired, shifting towards a state of hypoacetylation. The histone hyperacetylation produced by direct inhibition of HDACs leads to neuroprotective actions. This review attempts to elaborate on role of small molecule inhibitors of HDACs on neuronal differentiation and throws light on the potential of HDAC inhibitors as therapeutic agents for treatment of neurodegenerative diseases. The role of HDACs in neuronal cellular and disease models and their modulation with HDAC inhibitors are also discussed. Significance of these HDAC inhibitors has been reviewed on the process of neuronal differentiation, neurite outgrowth and neuroprotection regarding their potential therapeutic application for treatment of neurodegenerative diseases.

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive and fatal neurodegenerative disease that leads to a loss of muscle control due to nerve cells being affected in the brain and spinal cord. Some of the common clinical presentations of ALS include weakness of muscles, changes in behavior, dysfunction in speech, and cognitive difficulties. The cause of ALS is uncertain, but through several studies, it is known that mutations in SOD1 or C9orf72 genes could play a role as a factor of ALS. In addition, studies indicate that an excessive amount of free radicals, the reactive oxygen species (ROS), leads to neuronal damage by the peroxidation of unsaturated fatty acids in the neuronal cells. Edaravone, the newly approved antioxidant drug for ALS, halts the progression of ALS in the early stages through its cytoprotective effect and protects the nerves by reducing ROS. In this review, different aspects of ALS will be discussed, including its pathology, genetic aspect, and diagnosis. This review also focuses on edaravone as a treatment option for ALS, its mechanism of action, and its pharmacological properties. Clinical trials and adverse effects of edaravone and care for ALS patient are also discussed.

Alzheimer’s disease is a neurodegenerative condition leading to atrophy of the brain and robbing nearly 5.8 million individuals in the United States age 65 and older of their cognitive functions. Alzheimer’s disease is associated with dementia and a progressive decline in memory, thinking, and social skills, eventually leading to a point that the individual can no longer perform daily activities independently. Currently available drugs on the market temporarily alleviate the symptoms, however, they are not successful in slowing down the progression of Alzheimer’s disease. Treatment and cures have been constricted due to the difficulty of drug delivery to the blood-brain barrier. Several studies have led to identification of vesicles to transport the necessary drugs through the blood-brain barrier that would typically not achieve the targeted area through systemic delivered medications. Recently, liposomes have emerged as a viable drug delivery agent to transport drugs that are not able to cross the blood-brain barrier. Liposomes are being used as a component of nanoparticle drug delivery; due to their biocompatible nature; and possessing the capability to carry both lipophilic and hydrophilic therapeutic agents across the blood brain barrier into the brain cells. Studies indicate the importance of liposomal based drug delivery in treatment of neurodegenerative disorders. The idea is to encapsulate the drugs inside the properly engineered liposome to generate a response of treatment. Liposomes are engineered to target specific diseased moieties and also several surface modifications of liposomes are under research to create a clinical path to the management of Alzheimer’s disease. This review deals with Alzheimer’s disease and emphasize on challenges associated with drug delivery to the brain, and how liposomal drug delivery can play an important role as a drug delivery method for the treatment of Alzheimer’s disease. This review also sheds some light on variation of liposomes. Additionally, it emphasizes on the liposomal formulations which are currently researched or used for treatment of Alzheimer’s disease and also discusses the future prospect of liposomal based drug delivery in Alzheimer’s disease.

Inherited retinal disorders (IRDs) represent a group of challenging genetic conditions that often lead to severe visual impairment or blindness. The complexity of these disorders, arising from their diverse genetic causes and the unique structural and functional aspects of retinal cells, has made developing effective treatments particularly challenging. Recent advancements in gene therapy, especially non-viral nucleic acid delivery systems like liposomes, solid lipid nanoparticles, dendrimers, and polymersomes, offer promising solutions. These systems provide advantages over viral vectors, including reduced immunogenicity and enhanced targeting capabilities. This review delves into introduction of common IRDs such as Leber congenital amaurosis, retinitis pigmentosa, Usher syndrome, macular dystrophies, and choroideremia and critically assesses current treatments including neuroprotective agents, cellular therapy, and gene therapy along with their limitations. The focus is on the emerging role of non-viral delivery systems, which promise to address the current limitations of specificity, untoward effects, and immunogenicity in existing gene therapies. Additionally, this review covers recent clinical trial developments in gene therapy for retinal disorders.

Backgrounds: Antibody–drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the cytotoxic potency of drugs, representing a significant class of targeted cancer therapeutics. Despite their clinical success, formulation-related instability, rather than biological inefficacy, is a major contributing factor to setbacks in ADC development. This review examines the biochemical, physicochemical, and formulation factors that contribute to ADC stability, with a focus on excipient selection, conjugation site heterogeneity, and linker–payload reactivity. Methods: This comprehensive review was based on a selection of peer-reviewed mechanistic, analytical, and manufacturability studies on ADC stability. Our goal was to highlight formulation strategies, degradation pathways, and solid-state stabilization principles that affect the pharmacokinetics and therapeutic efficacy of ADC. Results: Results demonstrate how formulation variability including buffer composition, excipient choice, ionic strength, and lyophilization can directly affect payload release, linker cleavage, kinetics, and antibody conformation. It has been demonstrated that techniques, such as lyophilization with glass-forming matrices and the addition of surfactants, enhance stability against hydrolysis, oxidation, and aggregation. Developments in analytical characterization, such as real-time kinetic modeling and multi-attribute techniques based on mass spectrometry, have made quantification of degradation and bioactivity losses more predictable in ADC formulations. The connection between chemical stability and formulation outcomes is being redefined by new techniques, such as model-informed optimization and AI-driven design. Conclusions: ADC formulation is now a key component of molecular stability, clinical reliability, and regulatory compliance rather than a secondary consideration. By guaranteeing long-term stability, better pharmacokinetics, and improved therapeutic indices across next-generation designs, these approaches have the potential to revolutionize ADC development.

Objectives: Traditional 2D in vitro models often fail to recapitulate the complex architecture and microenvironment of the human midbrain, limiting their translational relevance in drug discovery for neurological disorders such as Parkinson’s disease (PD). To address this, 3D culture systems are gaining traction due to their improved physiological relevance. However, advanced 3D models such as organoids and assembloids often suffer from reduced reproducibility and increased methodological complexity, making them less suitable for early-stage drug screening. Our objective was to develop a streamlined and reproducible 3D Neurosphere-based method for generating midbrain-like spheroids. Methods: We developed 3D Neural Progenitor Cells (NPCs) neurospheres using U-bottom ultra-low attachment plates. NPCs (12,800 cells/well) were seeded in (ULA) 96-well plates, cultured in NPC expansion media for 3 days, and then transitioned to a dopaminergic differentiation medium for 21 days. Immunostaining was performed to check for midbrain differentiation and presence of dopaminergic markers and ELISA was used to quantify α-synuclein levels in both 2D and 3D NPC cultures. Results: Resulting spheroids averaged 210 μm in diameter and were maintained in culture for up to 70 days. Immunostaining confirmed expression of midbrain and dopaminergic markers (FOXA2, DAT), while ELISA quantification revealed elevated α-synuclein levels compared to 2D cultures. Conclusions: This Neurosphere-based model provides a straightforward and scalable platform for the generation and differentiation of NPC-derived spheroids, enabling consistent spheroid measurement and characterization of α-synuclein levels, thereby supporting its utility in preclinical drug or neuroprotective compound screening applications for Parkinson disease.