With the progression of investigations on the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), neurological complications have emerged as a critical aspect of the ongoing coronavirus disease 2019 (Covid‐19) pandemic. Besides the well‐known respiratory symptoms, many neurological manifestations such as anosmia/ageusia, headaches, dizziness, seizures, and strokes have been documented in hospitalised patients. The neurotropism background of coronaviruses has led to speculation that the neurological complications are caused by the direct invasion of SARS‐CoV‐2 into the nervous system. This invasion is proposed to occur through the infection of peripheral nerves or via systemic blood circulation, termed neuronal and haematogenous routes of invasion, respectively. On the other hand, aberrant immune responses and respiratory insufficiency associated with Covid‐19 are suggested to affect the nervous system indirectly. Deleterious roles of cytokine storm and hypoxic conditions in blood‐brain barrier disruption, coagulation abnormalities, and autoimmune neuropathies are well investigated in coronavirus infections, as well as Covid‐19. Here, we review the latest discoveries focussing on possible molecular mechanisms of direct and indirect impacts of SARS‐CoV‐2 on the nervous system and try to elucidate the link between some potential therapeutic strategies and the molecular pathways.

Neuronal loss is one of the striking causes of various central nervous system (CNS) disorders, including major neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and Amyotrophic lateral sclerosis (ALS). Although these diseases have different features and clinical manifestations, they share some common mechanisms of disease pathology. Progressive regional loss of neurons in patients is responsible for motor, memory, and cognitive dysfunctions, leading to disabilities and death. Neuronal cell death in neurodegenerative diseases is linked to various pathways and conditions. Protein misfolding and aggregation, mitochondrial dysfunction, generation of reactive oxygen species (ROS), and activation of the innate immune response are the most critical hallmarks of most common neurodegenerative diseases. Thus, endoplasmic reticulum (ER) stress, oxidative stress, and neuroinflammation are the major pathological factors of neuronal cell death. Even though the exact mechanisms are not fully discovered, the notable role of mentioned factors in neuronal loss is well known. On this basis, researchers have been prompted to investigate the neuroprotective effects of targeting underlying pathways to determine a promising therapeutic approach to disease treatment. This review provides an overview of the role of ER stress, oxidative stress, and neuroinflammation in neuronal cell death, mainly discussing the neuroprotective effects of targeting pathways or molecules involved in these pathological factors.