Parkinson's disease (PD) is a prevalent neurodegenerative disorder resulting from the degeneration of dopamenergic neurons in the substantia nigra pars compacta (SNpc). Research has predominantly centered on understanding the dysfunction of dopaminergic neurotransmission in PD. Recently, more studies discussed the potential role of other neurotransmitters in PD neuropathology. One of the most important non-dopaminergic neurotransmitters involved in the pathogenesis of PD is glutamate, which is widely involved in glutamatergic neurotransmission in different brain regions, including SNpc. The development and progression of PD neuropathology and levodopa-induced dyskinesias (LID) are associated with glutamate neurotoxicity. Therefore, this review seeks to explore the possible involvement of glutamatergic signaling in PD development and assess the therapeutic potential of glutamate receptor antagonists in treating the disorder.

Alzheimer disease (AD) is a progressive neurodegenerative disease marked by the accumulation of extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles containing tau protein. Given the relentless deterioration in AD, strategies to slow its progression often focus on inhibiting Aβ production or aggregation. However, numerous clinical trials targeting Aβ in later disease stages have shown limited success in reversing cognitive decline, potentially due to intervening too late in the disease course. Emerging evidence suggests that addressing Aβ pathology during the earliest phases of AD, before the occurrence of neuronal damage, may be beneficial for preserving cognitive function. Thus, therapeutic approaches aimed at reducing Aβ levels, such as anti-Aβ antibodies, are likely to yield greater benefits when implemented early in the disease trajectory. Such evidence underscores the rationale for prioritizing early-stage interventions in AD drug development. However, disrupting the physiological role of Aβ, which plays a role in normal brain function, might inadvertently worsen clinical outcomes, highlighting the need for nuanced therapeutic strategies. Therefore, this review aims to explore the dual aspects of Aβ biology: its natural role in the brain and the potential of anti-Aβ immunotherapy, particularly targeting amyloid plaques, as a promising avenue for modifying AD progression when timed appropriately. SIGNIFICANCE STATEMENT: This review highlights that β-amyloid (Aβ) has a dual role in both supporting synaptic plasticity and memory via nicotinic receptor activation and driving Alzheimer disease neuropathology, emphasizing that early-stage Aβ-targeted immunotherapy may prevent cognitive decline while preserving the neuroprotective functions of Aβ, thereby refining therapeutic strategies and advancing understanding of the complex role of Aβ in neural health and disease.

Neurogenesis is a complex process by which the neurons and supporting cells of the central nervous system (CNS) are generated by neural stem cells. Adult hippocampal neurogenesis (AHN) in the human brain is an active process during life and plays a critical role in the regulation of memory, cognition, and mood. It has been shown that epilepsy is linked with dysregulation of AHN. Of note, AHN is very sensitive to the pathological electrical stimuli during epileptic seizures, which result in the induction of neurogenesis in acute epilepsy and inhibition of neurogenesis in chronic epilepsy. Epileptic seizure-induced neurodegeneration activates the mobilization of neural stem cells during neurogenesis to substitute for neural loss in temporal lobe epilepsy (TLE), which is the most refractory type of epilepsy. Moreover, recurrent epileptic seizures in TLE trigger neurogenesis in certain brain regions. However, AHN is a transient acute epileptic seizure that terminated with 1-4 weeks following status epilepticus (SE). Nevertheless, adult AHN is dramatically reduced in chronic epilepsy and associated with the development of cognitive impairment in TLE. These findings indicate that impairment of AHN is linked with the severity of epileptic seizures. Hence, neurogenesis activators may attenuate the pathogenesis of TLE. Therefore, this review aims to discuss and explain the beneficial role of AHN in TLE and how neurogenesis activators could be effective in the management of epilepsy.