Abstract: Neurodegenerative diseases (NDDs) are a class of disorders characterized by the gradual loss or malfunction of specific cell populations in the nervous system, which can be triggered by genetic or environmental factors. As a result, patients often experience a decline in mobility, sensation, memory, and cognition, which can ultimately lead to a fatal outcome. The global incidence of NDDs, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis (ALS), and multiple sclerosis, is increasing. Many NDDs are associated with aging, and they pose significant challenges to affected families, healthcare systems, and societies, which will only be exacerbated by the current demographic megatrend. Clinical management of NDDs is primarily focused on mitigating physical or mental impairment, slowing disease progression, and providing palliative care. Despite extensive research efforts spanning decades, there are currently no effective cures for NDDs. This is largely due to a limited understanding of disease mechanisms, the heterogeneity of the pathophysiology, and the failure to identify specific pathways and molecular targets that cause the diseases. For example, most ALS cases are sporadic without clear-cut genetic cause and a unique patient-specific etiology. Disease-associated cell types, such as neurons in the patient’s brain, are not easily accessible for clinical evaluations. The lack of patient biopsies and the scarcity of representative animal models hinder mechanistic studies and the discovery of potential treatments.